Research ArticleCancer

Stromal Endothelial Cells Directly Influence Cancer Progression

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Science Translational Medicine  19 Jan 2011:
Vol. 3, Issue 66, pp. 66ra5
DOI: 10.1126/scitranslmed.3001542

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Not Just Wallflowers After All

Teen movies like Mean Girls and Never Been Kissed remind us that every school has its wallflowers—kids who are always present, but serve as wallpaper at social functions. Yet, if one takes the time to talk with them, some wallflowers turn out to be the most interesting guests at the gala. Lining the walls of blood vessels, endothelial cells have long been thought to be the wallflowers of tumors—providing support but not having a clearly defined, active role in tumor growth and metastasis. Now, Franses et al. have found that, instead, endothelial cells are the life of the party in the tumor microenvironment, secreting molecules that dynamically regulate cancer cell proliferation and invasiveness.

The authors explored the effects of secretions from quiescent endothelial cells—ones that have exited the cell cycle—on tumors both in vitro and in a mouse model of lung adenocarcinoma. They found that endothelial cells produced molecules that blocked proliferation and invasiveness of both breast and lung cancer cells in vitro, perhaps by reducing signaling through intracellular pro-tumor and pro-inflammatory pathways. Inhibiting endothelial cell production of perlecan, which is a component of the extracellular matrix, blocked this effect on tumor cell invasiveness in a manner that was dependent on the pro-inflammatory cytokine interleukin-6. Indeed, in vivo transplantation of quiescent endothelial cells embedded in a porous matrix curbed tumor growth, and perlecan was required for metastatic inhibition by endothelial secretions. These observations suggest that endothelial cells do not just hang around in the background providing support, but are active participants in and potential targets for regulating the tumor microenvironment. Endothelial cell–cancer interactions add to the emerging appreciation of stromal-cancer crosstalk, and may enable exciting, novel therapies for malignant diseases.

Footnotes

  • Citation: J. W. Franses, A. B. Baker, V. C. Chitalia, E. R. Edelman, Stromal Endothelial Cells Directly Influence Cancer Progression. Sci. Transl. Med. 3, 66ra5 (2011).

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