Metastasis remains the overwhelming cause of death for cancer patients. During metastasis, cancer cells will leave the primary tumor, intravasate into the bloodstream, arrest at a distant organ, and eventually develop into gross lesions at the secondary sites. This intricate process is influenced by innumerable factors and complex cellular interactions described in 1889 by Stephen Paget as the seed and soil hypothesis. In this review, we revisit this seed and soil hypothesis with an emerging understanding of the cancer cell (i.e. seed) and its microenvironment (i.e. soil). We will provide background to suggest that a critical outcome of the seed-soil interaction is resistance of the stresses that would otherwise impede metastasis.
"The NI ability of hilar-CCA was evaluated by hilar-CCA and perineural cells coculture migration assay with three replicates. Hilar-CCA cells was cocultured with perineural cells using Matrigel invasion chamber purchased from BD Biocoat Cellware (San Jose, CA, USA) as previously reported.18 Medium (0.5 µL) containing 5×105 hilar-CCA cells was added to the upper chamber, and 0.5 mL of either medium alone or medium containing 1 to 2×104 HPC cells was added to the lower chamber. "
[Show abstract][Hide abstract] ABSTRACT: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing.
An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay.
The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation.
CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.
Gut and Liver 03/2014; 8(2):196-204. DOI:10.5009/gnl.2014.8.2.196 · 1.81 Impact Factor
"It is well established that the reciprocal interaction of tumour cells with local bone stroma at the metastatic site plays a critical role in metastatic dissemination in prostate cancer (PCa)
[1,2]. To-date however, studies have not yet addressed how at the cellular level, these tumour-stromal interactions affect important protein constituents implicated in metastatic dissemination including epithelial-to-mesenchymal transition (EMT) proteins and chemokine receptor expression. "
[Show abstract][Hide abstract] ABSTRACT: The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediating tumour-stromal interactions.
Utilising 3D in vitro assays we evaluated and compared 1. Monocultures of prostate metastatic PC3, bone stromal derived HS5 and prostate epithelial RWPE-1 cells and 2. Tumour-stromal co-cultures (PC3 + HS5) to ascertain changes in cellular phenotype, function and expression of metastatic markers.
In comparison to 3D monocultures of PC3 or HS5 cells, when cultured together, these cells displayed up-regulated invasive and proliferative qualities, along with altered expression of epithelial-to-mesenchymal and chemokine protein constituents implicated in metastatic dissemination. When co-cultured, HS5 cells were found to re-express N-Cadherin and chemokine receptor CXCR7. Alterations in N-Cadherin expression were found to be mediated by soluble factors secreted by PC3 tumour cells, while chemokine receptor re-expression was dependent on direct cell-cell interactions. We have also shown that integrins beta 1 and alpha 6 play an integral role in maintaining cell homeostasis and mediating expression of E-Cadherin, N-Cadherin and vimentin, in addition to chemokine receptor CXCR7.
Collectively our results suggest that both PC3 and HS5 cells provide a "protective" and reciprocal milieu that promotes tumour growth. As such 3D co-cultures may serve as a more complex and valid biological model in the drug discovery pipeline.
Molecular Cancer 09/2013; 12(1):112. DOI:10.1186/1476-4598-12-112 · 4.26 Impact Factor
"Indeed, while DM is a paraneoplastic syndrome occasionally associated with colon carcinoma [3, 6], the molecular mechanism responsible for its development depends on the cross-reactivity between antigens expressed by cancer cells and regenerating fibers . Furthermore, several lines of evidence suggest that inflammation and activation of the immune response represent favorable microenvironments for tumor cell invasion and dissemination [10, 11]. Thus, it is intriguing to speculate that the inflammatory and the immune responses that boost paraneoplastic DM may provide a favorable milieu for tumor cell invasion and metastasization to skeletal muscles, likely reverting the hostile environment that in nature characterizes muscle tissues. "
[Show abstract][Hide abstract] ABSTRACT: Skeletal muscle metastases are very rare events in colorectal carcinoma. By contrast, dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations and a well-recognized association with several human malignancies and, among others, colorectal cancer. Here, we report the case of a 71-year-old woman with paraneoplastic dermatomyositis followed by the development of a metastatic colon cancer. Interestingly, this patient developed multiple skeletal metastases which were preceded by the worsening of systemic symptoms of dermatomyositis. This observation suggests that, while muscle tissue is usually resistant to the development of tumor metastases, the inflammatory and immune response which characterizes and boosts paraneoplastic myopathy may represent a favorable soil for tumor cell invasion and metastasization to skeletal muscles.
Case Reports in Medicine 07/2013; 2013:392609. DOI:10.1155/2013/392609
Daxing Xie, Liang Liu, Hasan Osaiweran, Chaoran Yu, Fang Sheng, Chun Gao, Junbo Hu, Jianping Gong,
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