The Colorectal Tumor Microenvironment The Next De

Authors: Nicole Beauchemin

Publish Date: 2011/07/07

Volume: 4, Issue: 2, Pages: 181-

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Abstract

Colorectal cancer cells establish a crosstalk with the tumor microenvironment such that implantation and development of the tumor is generally favoured CRC progression depends on mutations in the tumor’s oncogenic pathways as well as metastasis suppressor genes but is also influenced by the inflammatory components in the microenvironment Inflammation results from the dietary intakes and is either compounded or counterbalanced by our lifestyles Whether driven by intrinsic pathways or infection inflammation produces a massive influx of cytokines and chemokines Currently in colorectal cancer the best approach to counter this inflammatory wave in the microenvironment appears to be CCL2 cytokine targeting A fairly new avenue of discovery has identified microRNAs regulating colorectal cancermediated inflammation and in particular the IL6 proinflammatory pathway that induces proapoptotic genes and HIF1αelicited VEGF secretion miRNAs also play a significant role in controlling metabolic genes such as the upregulation of the fatty acid synthase gene with the concomitant downregulation of the carnitine palmitoyl transferase 1 gene Within the metastatic environment the Discoidin domain receptor2 DDR2 gene encodes a tyrosine kinase receptor for fibrillar collagen that contributes to colorectal cancer metastasis by increasing myofibroblasts neoangiogenic vessels and proliferating cancer cells Ongoing identification of gene signatures differentiating between primary tumor cells and their metastatic counterparts promises a wealth of new targets to be exploited for further therapeutic use within the next decade

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