Tumor growth and cancer development are considered clear examples of Darwinian selection, whereby random mutational events in heterogeneous cancer cell populations that best fit the selective microenvironment are preferred.(1) As a result, cancer cells evolve resistance to apoptosis, hide from immune surveillance and acquire the ability to invade other organs. Cancer cells, however, are not necessarily passive subjects of selection; they can actively subvert the host tissue to provide a favorable habitat for their growth. Recent findings by Calon et al. convincingly demonstrate that transforming growth factor-β-induced secretion of interleukin 11 by tumor stromal fibroblasts is a necessary prerequisite for the development of distant metastases in colorectal carcinoma. Thus, understanding the complex molecular feedback loops between cancer cells and the surrounding microenvironment (i.e., the tumor-associated stroma or invaded host tissue) should aid the identification of useful molecular targets for improving clinical management of advanced metastatic cancers.

Department of Histology and Embryology; Faculty of Medicine; Masaryk University; Brno Czech Republic

Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, et al. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22:571–84. doi: 10.1016/j.ccr.2012.08.013. PubMed

See more in PubMed

Gillies RJ, Verduzco D, Gatenby RA. Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat Rev Cancer. 2012;12:487–93. doi: 10.1038/nrc3298. PubMed DOI PMC

Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8. doi: 10.1038/nrc1098. PubMed DOI

Marsh T, Pietras K, McAllister SS. Fibroblasts as architects of cancer pathogenesis. Biochim Biophys Acta. 2012 In press. PubMed PMC

Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67. doi: 10.1016/0092-8674(90)90186-I. PubMed DOI

Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, Papavassiliou AG. TGF-beta signalling in colon carcinogenesis. Cancer Lett. 2012;314:1–7. doi: 10.1016/j.canlet.2011.09.041. PubMed DOI

Bacman D, Merkel S, Croner R, Papadopoulos T, Brueckl W, Dimmler A. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study. BMC Cancer. 2007;7:156. doi: 10.1186/1471-2407-7-156. PubMed DOI PMC

Fritzmann J, Morkel M, Besser D, Budczies J, Kosel F, Brembeck FH, et al. A colorectal cancer expression profile that includes transforming growth factor beta inhibitor BAMBI predicts metastatic potential. Gastroenterology. 2009;137:165–75. doi: 10.1053/j.gastro.2009.03.041. PubMed DOI

Xu WQ, Jiang XC, Zheng L, Yu YY, Tang JM. Expression of TGF-beta1, TbetaRII and Smad4 in colorectal carcinoma. Exp Mol Pathol. 2007;82:284–91. doi: 10.1016/j.yexmp.2006.10.011. PubMed DOI

Zhang B, Halder SK, Zhang S, Datta PK. Targeting transforming growth factor-beta signaling in liver metastasis of colon cancer. Cancer Lett. 2009;277:114–20. doi: 10.1016/j.canlet.2008.11.035. PubMed DOI PMC

Lin L, Liu A, Peng Z, Lin HJ, Li PK, Li C, et al. STAT3 is necessary for proliferation and survival in colon cancer-initiating cells. Cancer Res. 2011;71:7226–37. doi: 10.1158/0008-5472.CAN-10-4660. PubMed DOI PMC

Isaacs C, Robert NJ, Bailey FA, Schuster MW, Overmoyer B, Graham M, et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 1997;15:3368–77. PubMed

Wilde MI, Faulds D. Oprelvekin: a review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia. BioDrugs. 1998;10:159–71. doi: 10.2165/00063030-199810020-00006. PubMed DOI

Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell. 2012;148:349–61. doi: 10.1016/j.cell.2011.11.025. PubMed DOI PMC