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The Colorectal Tumor Microenvironment: The Next Decade

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Cancer Microenvironment

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 cancer-mediated inflammation, and in particular the IL-6 pro-inflammatory pathway that induces pro-apoptotic genes and HIF1α-elicited 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 down-regulation of the carnitine palmitoyl transferase 1 gene. Within the metastatic environment, the Discoidin domain receptor-2 (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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Acknowledgment

Work in Dr. Beauchemin’s laboratory is funded through the Canadian Institutes of Health Research and the Cancer Research Society Inc.

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Authors and Affiliations

  1. Goodman Cancer Research Centre, McGill University, McIntyre Building, Lab. 708, 3655 Promenade Sir-William-Osler, Montreal, QC, Canada, H3G 1Y6

    Nicole Beauchemin

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  1. Nicole Beauchemin
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Correspondence to Nicole Beauchemin.

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Beauchemin, N. The Colorectal Tumor Microenvironment: The Next Decade. Cancer Microenvironment 4, 181–185 (2011). https://doi.org/10.1007/s12307-011-0074-7

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  • DOI: https://doi.org/10.1007/s12307-011-0074-7

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