Clotilde Costa

Clotilde Costa
Instituto de Investigación Sanitaria de Santiago de Compostela | IDIS · Liquid Biopsy Lab (Roche-Chus Joint Unit)

PhD

About

50
Publications
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645
Citations
Additional affiliations
August 2015 - October 2016
Instituto de Investigación Sanitaria de Santiago de Compostela
Position
  • PhD Research
November 2006 - November 2013

Publications

Publications (50)
Preprint
Metastasis is the primary cause of death for most breast cancer patients who succumb to the disease. During the haematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are micro-environmental and systemic processes contributing to cancer regulation. We have published that Red Blood Cells (RBCs) tha...
Article
Full-text available
Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify t...
Article
Full-text available
Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2− BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic di...
Preprint
Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic di...
Preprint
Full-text available
Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify th...
Article
Full-text available
CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metas...
Preprint
Full-text available
Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. C...
Preprint
Full-text available
Background: CTCs have extensively used for the monitoring and characterization of metastatic prostate cancer, but their use in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metast...
Article
Full-text available
The culture and expansion of circulating tumor cells (CTCs) for ex vivo assays plays an important role in precision medicine. However, it still represents a big challenge in translational research. Generating knowledge about the characteristics of CTCs can help to shed light about the metastasis process. Furthermore, ex vivo culture of CTCs might a...
Article
Full-text available
Circulating tumor cell (CTC) enumeration has emerged as a powerful biomarker for the assessment of prognosis and the response to treatment in metastatic breast cancer (MBC). Moreover, clinical evidences show that CTC-cluster counts add prognostic information to CTC enumeration, however, their significance is not well understood, and more clinical e...
Chapter
The majority of deaths related to breast cancer are caused by metastasis. Understanding the process of metastasis is key to achieve a reduction on breast cancer mortality. Currently, liquid biopsies are gaining attention in this regard. Circulating tumor cells (CTCs), an important component of liquid biopsies, are cells shed from primary tumor that...
Article
Full-text available
The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be t...
Article
Full-text available
Liquid biopsy offers unique opportunities for low invasive diagnosis, real-time patient monitoring and treatment selection. The phenotypic and molecular profile of circulating tumor cells (CTCs) can provide key information about the biology of tumor cells, contributing to personalized therapy. CTC isolation is still challenging, mainly due to their...
Article
Full-text available
Triple‐negative breast cancer (TNBC) is characterized by high rates of metastasis and no available molecular targets. CTCs derived xenografts (CDX) have demonstrated to be a promising tool for understanding cancer biology. In this study a CDX from a TNBC patient was developed for the first time. After CDX characterization, WNT signalling was found...
Article
Full-text available
The high rates of tumor recurrence and progression represent a major clinical problem in non-muscle invasive bladder cancer. Previous data showed that EZH2-dependent signaling mediates these processes, whereas the frequent alterations of PIK3CA gene (copy gains and mutations) are predictive of reduced recurrence. Here we show, using clinical sample...
Article
Full-text available
Circulating tumour cells (CTCs) play a key role in the metastasis process, as they are responsible for micrometastasis and are a valuable tool for monitoring patients in real-time. Moreover, efforts to develop new strategies for CTCs isolation and characterisation, and the translation of CTCs into clinical practice needs to overcome the limitation...
Data
Flow cytometry analysis. A) Summary of Median Fluorescence Intensity of flow cytometer analysis of listed cell lines and markers. B) Flow cytometry analysis of SW480 and MDA-MB-231 cells incubated with anti-EpCAM (in blue), anti-EGFR (in orange) antibody or unlabelled cells (in red). (TIF)
Data
Characteristics of human tumor cell lines. (DOC)
Article
Full-text available
E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided into two groups:...
Article
Full-text available
Bladder cancer (BC) is a highly prevalent human disease in which retinoblastoma (Rb) pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Retinoblastoma (Rb) family genes in the mouse urothelium is sufficie...
Article
Background: Remodeling targeted tissues for reception of tumor cells metastasizing from primary lesions is a consequence of communication between the tumor and the environment that governs metastasis. This study describes a novel approach that aims to disrupt the process of metastasis by interfering with this intense dialogue. Methods: Proteomic...
Article
Full-text available
Metastasis is the cause of most cancer deaths. Circulating tumour cells (CTCs) are cells released from the primary tumour into the bloodstream that are considered the main promoters of metastasis. Therefore, these cells are targets for understanding tumour biology and improving clinical management of the disease. Several techniques have emerged in...
Article
Full-text available
The Rb1 gene was the first bona fide tumor suppressor identified and cloned more than 25 years ago. Since then, a plethora of studies have revealed the functions of pRb and the existence of a sophisticated and strictly regulated pathway that modulates such functional roles. An emerging paradox affecting Rb1 in cancer connects the relatively low num...
Article
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The catalytic activity of GDP/GTP exchange factors (GEFs) is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily...
Article
Full-text available
The specific ablation of Rb1 gene in stratified epithelia (Rb(F/F);K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues; however, Rb(F/F);K14cre;p107(-/-) mice die postnatally. Here we show, using an inducible m...
Article
The specific ablation of Rb1 gene in epidermis (Rb(F/F);K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1...
Article
Full-text available
Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demon...
Article
We have analyzed the role of the thyroid hormone receptors (TRs) in epidermal homeostasis. Reduced keratinocyte proliferation is found in interfollicular epidermis of mice lacking the thyroid hormone binding isoforms TRα1 and TRβ (KO mice). Similar results were obtained in hypothyroid animals, showing the important role of the liganded TRs in epide...
Article
Situations in which epidermal mutant mice display early lethality after birth are rather frequent. This condition precludes any kind of analysis of adult or even newborn mice tissues. We propose the in vivo embryonic skin transplantation as an alternative to solve this problem. This method allows the generation of a stable epidermal tissue that mim...
Article
Full-text available
The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular...
Article
Full-text available
Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. W...
Article
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Increased ST6Gal I activity has been associated with the alpha(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaalpha(2,6)Galbeta(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with...
Article
The specific ablation of Trp53 gene in mouse epidermis leads to the spontaneous development of aggressive squamous cell carcinoma, a process that is accelerated by the subsequent loss of Rb gene. The possible mechanisms leading to spontaneous tumor formation in epidermis in the absence of Trp53 were studied focusing on hair cycle defects, inflammat...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia, of poor prognosis and survival, which frequently displays Akt overactivation. Previously, we reported that mice expressing high levels of constitutively Akt activity (myrAkt) in oral epithelia develop lesions and tumors in the oral cavity. Functional genomics of primary kera...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia with poor prognosis and survival that frequently displays Akt overactivation. Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC. The myrAkt mice dev...

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Project (1)
Project
The use of nanotechnology and nano-materials for the development of new nano-systems that enable the diagnosis, evaluation and monitoring of cancer