George Karagiannis

George Karagiannis
Albert Einstein College of Medicine | AECOM · Department of Microbiology & Immunology

DVM, PhD

About

112
Publications
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2,178
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Publications

Publications (112)
Article
Full-text available
The suppression of the bone morphogenetic protein (BMP) signaling pathway has been recently shown to promote adenoma-to-carcinoma transition in sporadic colon cancer. However, its role in the evolution of early preneoplastic changes to neoplasia remains elusive. In the present study, we aimed to investigate the gene expression levels of multiple ex...
Article
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Abstract Bone morphogenetic proteins (BMP) are phylogenetically conserved signaling molecules of the transforming growth factor-beta (TGF-beta) superfamily of proteins, involved in developmental and (patho)physiological processes, including cancer. BMP signaling has been regarded as tumor-suppressive in colorectal cancer (CRC) by reducing cancer ce...
Article
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Bone morphogenetic proteins (BMPs) are a group of growth factors with dual functions in cancer development and progression. Recently, certain tumor-promoting roles have been identified for selected antagonists/inhibitors (BMPIs) of this developmental pathway. A recent focus on the implication of BMP in colorectal cancer progression has emerged, mai...
Article
It has been suggested that cancer-associated fibroblasts (CAFs) positioned at the desmoplastic areas of various types of cancer are capable of executing a migratory program, characterized by accelerated motility and collective configuration. Since CAFs are reprogrammed derivatives of normal progenitors, including quiescent fibroblasts, we hypothesi...
Article
The cancer invasion front (CIF), a spatially-recognized area due to the frequent presence of peritumoral desmoplastic reaction, represents a cancer site where many hallmarks of cancer metastasis occur. It is now strongly suggested that the desmoplastic microenvironment holds crucial information for determining tumor development and progression. Des...
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Metastatic dissemination in breast cancer is regulated by specialized intravasation sites called “tumor microenvironment of metastasis” (TMEM) doorways, composed of a tumor cell expressing the actin-regulatory protein Mena, a perivascular macrophage, and an endothelial cell, all in stable physical contact. High TMEM doorway number is associated wit...
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Epidemiologic data suggest that cancer survivors tend to develop a protuberant number of adverse late effects, including second primary malignancies (SPM), as a result of cytotoxic chemotherapy. Besides the genotoxic potential of these drugs that directly inflict mutational burden on genomic DNA, the precise mechanisms contributing to SPM developme...
Article
The Cxcl12/Cxcr4 signaling axis has been shown to promote metastasis in multiple mouse models of breast carcinoma and to be associated with increased metastatic risk in humans. Indeed, prior studies have specifically linked Cxcl12/Cxcr4 to breast cancer cell seeding, homing, survival and proliferation at future metastatic sites, due to the aberrant...
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Immune cells are a major constituent of the tumor microenvironment, and participate in interactions with tumor cells to promote the acquisition of critical hallmarks of cancer [...]
Article
Background: Black race is associated with worse outcome in patients with breast cancer. The distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in National Cancer Institute-sponsored clinical trial was evaluated. Methods: Pooled data were analyzed from 8 National Surgical Adjuvant Brea...
Article
Exosomes comprise a subtype of extracellular vesicles involved in cell-to-cell communication, specifically by transporting biological molecules, such as proteins and nucleic acids, to either local or more distant recipient cells, thus triggering distinct biological behaviors. Included in the exosome cargo is frequently a wide range of proteolytic e...
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Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lu...
Preprint
Background: Black race is associated with worse outcome in patients with breast cancer. We evaluated distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in NCI-sponsored clinical trials. Methods: We analyzed pooled data from eight National Surgical Adjuvant Breast and Bowel Project (NSABP...
Article
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Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. Here, we employ high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is...
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The Tie2 receptor tyrosine kinase is expressed in vascular endothelial cells, tumor-associated macrophages, and tumor cells and has been a major focus of research in therapies targeting the tumor microenvironment. The most extensively studied Tie2 ligands are Angiopoietin 1 and 2 (Ang1, Ang2). Ang1 plays a critical role in vessel maturation, endoth...
Conference Paper
Background: The purpose of this study was to evaluate whether there are differences in distant recurrence rates between Black and White women with localized breast cancer who participated in NCI-sponsored clinical trials, and thus had access to state of the art oncologic care and lacked major comorbidities. Methods: We analyzed pooled data from 10...
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Although cancer immunotherapy has resulted in unpreceded survival benefits to subsets of oncology patients, accumulating evidence from preclinical animal models suggests that the immunosuppressive tumor microenvironment remains a detrimental factor limiting benefit for many patient subgroups. Recent efforts on lymphocyte-mediated immunotherapies ar...
Preprint
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Metastases are initiated by disseminated tumor cells (DTCs) that depart from the primary tumor and colonize target organs. Growing evidence suggests that the microenvironment of the primary tumor lesion primes DTCs to display dormant or proliferative fates in target organs. However, the manner in which events taking place in the primary tumor influ...
Article
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In primary breast tumors, cancer cells hematogenously disseminate through doorways in the vasculature composed of three-cell complexes (known as Tumor MicroEnvironment of Metastasis) comprising a perivascular macrophage, a tumor cell overexpressing the actin-regulatory protein Mammalian Enabled (Mena), and an endothelial cell, all in direct physica...
Preprint
Full-text available
Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. We employed high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the...
Article
Gliomas encompass highly invasive primary central nervous system (CNS) tumours of glial cell origin with an often poor clinical prognosis. Of all gliomas, glioblastoma is the most aggressive form of primary brain cancer. Current treatments in glioblastoma are insufficient due to the invasive nature of brain tumour cells, which typically results in...
Conference Paper
Background: Breast cancer cells use tumor microenvironment of metastasis (TMEM) doorways as portals for hematogenous dissemination to distant sites. Each TMEM doorway is composed of one perivascular macrophage in direct contact with one endothelial cell and one Mena expressing cancer cell. TMEM density is prognostic of metastatic outcome in breast...
Conference Paper
p> Background: Cancer stem cells (CSCs) play an important role during metastatic progression of breast cancer. However, little is known, at the single cell level, about the process of stemness induction in non-stem cells or the dynamic behavior of CSCs during hematogenous dissemination. Methods: Here, we employed high-resolution intravital multiph...
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Breast cancer is the second most commonly diagnosed cancer in American women following skin cancer. Despite overall decrease in breast cancer mortality due to advances in treatment and earlier screening, black patients continue to have 40% higher risk of breast cancer related death compared to white patients. This disparity in outcome persists even...
Article
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Doxorubicin remains an essential component of many cancer regimens, but its use is limited by lethal cardiomyopathy, which has been difficult to target, owing to pleiotropic mechanisms leading to apoptotic and necrotic cardiac cell death. Here we show that BAX is rate-limiting in doxorubicin-induced cardiomyopathy and identify a small-molecule BAX...
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Notch is an evolutionarily conserved signaling pathway with an important role in development and cell fate determination. Deregulation of Notch signaling has been associated with several pathological conditions, including cancer. Acting as an oncogene in some types of cancers and as a tumor suppressor in other, Notch effects seem to be highly conte...
Article
Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human malignancies and acts as a media...
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Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a...
Article
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Chemotherapy offers long-term clinical benefits to many patients with advanced cancer. However, recent evidence has linked the cytotoxic effects of chemotherapy with the de novo elicitation of a prometastatic tumor microenvironment. This "modified" tumor microenvironment is triggered by a chemotherapy-driven cytokine storm or through direct effects...
Conference Paper
Cancer stem cells (CSCs) play an important role during metastatic progression of breast cancer. However, the properties and dynamic behavior of CSCs are not well understood. Here, we employed high-resolution intravital multiphoton microscopy using a SOX2/OCT4 responsive fluorescent stem cell biosensor to directly observe CSC dynamics in the living...
Conference Paper
Cancer stem cells (CSCs) play an important role during metastatic progression of breast cancer. However, the properties and dynamic behavior of CSCs are not well understood. Here, we employed high-resolution intravital multiphoton microscopy using a SOX2/OCT4 responsive fluorescent stem cell biosensor to directly observe CSC dynamics in the living...
Article
Full-text available
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, NY, USA ² Integrated Imaging Program, Albert Einstein College of Medicine, NY, USA ³ Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, NY, USA ⁴ Department of Pathology, Albert Einstein College of Medicine, NY, USA Background: Chemotherapy has be...
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Macrophages represent a heterogeneous group of cells, capable of carrying out distinct functions in a variety of organs and tissues. Even within individual tissues, their functions can vary with location. Tumor‐associated macrophages (TAMs) specialize into three major subtypes that carry out multiple tasks simultaneously. This is especially true in...
Article
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Background Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, is not only essential for proper mammary ductal development, but also associated with breast cancer proliferation and growth. In the absence of AREG, mammary ductal growth is stunted and fails to expand. Furthermore, suppression of AREG expression in estrogen receptor...
Article
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Black race compared to white race is associated with more advanced stage and biologically aggressive breast cancer. Consequently, black patients are more frequently treated with neoadjuvant chemotherapy (NAC) than white patients. However, it is unclear how distant recurrence-free survival (DRFS) of black patients treated with NAC, compares to DRFS...
Article
Neoadjuvant chemotherapy (NAC) is used for treatment of localized breast cancer to decrease tumor size and improve surgical outcome. However, Karagiannis et al. (2017) has uncovered a previously unrecognized side-effect, which involves the induction of pro-metastatic changes in the primary breast cancer microenvironment, in response to NAC treatmen...
Article
Breast cancer is the most prevalent cancer in women worldwide and afflicts more than 3.1 million women in the US alone. The epidermal growth factor receptor (EGFR) is frequently overexpressed in breast cancer and is associated with poor clinical outcome. Several therapies involving anti-EGFR agents have been developed to target breast cancer. Howev...
Article
Neoadjuvant chemotherapy (NAC) induces influx of bone marrow-derived proangiogenic Tie2hi monocytes into the primary tumor, resulting in increased density of perivascular Tie2hi macrophages (1). Perivascular Tie2hi/Vegfhi macrophages in physical contact with Mena expressing cancer cells create micro-anatomic sites of transient vascular permeability...
Conference Paper
Background: Compared to white women, black women with operable breast cancer treated with primary surgical therapy and adjuvant or neoadjuvant systemic chemotherapy have higher recurrence rates and breast cancer mortality. Large randomized prospective studies did not find significant differences in distant-recurrence-free survival (DRFS) and overal...
Article
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Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a...
Article
Background: Compared to white women, black women with operable breast cancer treated with primary surgical therapy and adjuvant or neoadjuvant systemic chemotherapy have higher recurrence rates and breast cancer mortality. Large randomized prospective studies did not find significant differences in distant-recurrence free survival (DRFS) and overal...
Article
Full-text available
Stable, high-resolution intravital imaging of the lung has become possible through the utilization of vacuum-stabilized imaging windows. However, this technique is extremely invasive and limited to only hours in duration. Here we describe a minimally invasive, permanently implantable window for high-resolution intravital imaging of the murine lung...
Conference Paper
Neoadjuvant chemotherapy (NAC) is used for treatment of localized breast cancer to decrease tumor size and improve surgical outcome. However, our recent study has uncovered a previously unrecognized side effect of NAC, which involves the induction of pro-metastatic changes in the primary breast cancer microenvironment. In particular, NAC promotes t...
Article
Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal...
Article
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Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation and metastasis, which can offset the effects of chemotherapy, radiation, and anti-angiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cell...
Article
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Breast cancer cells disseminate through TIE2/MENACalc/MENAINV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we...
Article
Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been li...
Article
Full-text available
There is increasing consensus that cancer stem cells (CSC) play an important role during metastatic progression of breast cancer. Previous studies have shown that stem cells display a pro-invasive phenotype in breast cancer. However, the phenotypes specific to breast cancer stem cells have not been evaluated at single cell resolution in vivo. Here,...
Article
Chemotherapy induces influx of bone marrow-derived proangiogenic Tie2hi monocytes in primary tumors. Tie2hi perivascular macrophages specifically induce the prometastatic Mena isoforms in tumor cells and can assemble specialized microanatomical sites called “tumor microenvironment of metastasis” (TMEM), structures that may serve as doorways for int...
Article
Breast cancer is the most prevalent cancer in women worldwide and afflicts more than 3.1 million women in the US alone. The epidermal growth factor receptor (EGFR) is frequently overexpressed in breast cancer and is associated with poor clinical outcome. Several therapies involving anti-EGFR agents have been developed to target breast cancer. Howev...
Article
Numerous clinical studies have identified Tumor MicroEnvironment of Metastasis (TMEM) and MenaCalc as distinct but functionally interrelated prognostic indicators of distant metastasis in breast cancer patients. TMEM sites are the only sites where tumor cells intravasate in mammary tumors. TMEM score is calculated histologically as the density of t...
Article
Background: Breast cancer cell intravasation and dissemination occurs specifically at microanatomical structures that we call tumor-microenvironment of metastasis (TMEM), representing direct physical contact between a tumor cell expressing the actin-regulatory protein Mammalian-enabled (Mena), a perivascular Tie2hi/Vegfhi-expressing macrophage, and...
Article
Full-text available
Gene-expression profiling has yielded prognostic tests, such as MammaPrint and Oncotype Dx, which facilitate clinical decision-making in breast cancer patients. These tests are based on signatures constructed from whole tumor tissue, including tumor as well as stromal cells. Since metastatic tumor cells are not uniquely identified in these signatur...
Article
Chemotherapy induces influx of bone marrow-derived progenitors such as mesenchymal stem cells, endothelial progenitors and proangiogenic monocytes into the primary tumor to promote angiogenesis. Thus it is feared that chemotherapy may potentiate tumor cell invasion and metastasis. Here, we show that paclitaxel delays tumor growth in several mammary...
Article
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Gene expression profiling has yielded expression signatures from which prognostic tests can be derived to facilitate clinical decision making in breast cancer patients. Some of these signatures are based on profiling of whole tumor tissue (tissue signatures), which includes all tumor and stromal cells. Prognostic markers have also been derived from...
Article
Kallikrein-related peptidases (KLKs) represent the largest family of serine proteases within the human genome and are expressed in various tissues. Although they regulate several important physiological functions, KLKs have also been implicated in numerous pathophysiological processes, including cancer. Growing evidence describing the deregulation...
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Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs....