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Med Hypotheses. 2012 Jun;78(6):738-43. doi: 10.1016/j.mehy.2012.02.021. Epub 2012 Mar 28.

Enhanced vascular permeability is hypothesized to promote inflammation-induced carcinogenesis and tumor development via extravasation of large molecular proteins into the tissue.

Author information

1
Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, United States. Robert.carraway@umassmed.edu

Abstract

We propose that the growth of solid tumors is dependent, in part, on the entry of large molecular blood-borne growth regulators into the tissue and is facilitated by the highly permeable nature of tumor blood vessels. There is abundant evidence that the tumor vasculature is hyperpermeable and tumor growth is dependent on mediators that increase vascular permeability (e.g., VEGF and mast cells). Therefore, the extravasation of plasma proteins into the interstitial space could be an important determinant of tumor growth. Angiogenesis promotes cancer by creating a network of blood vessels that supplies oxygen and nutriment. A highly permeable vasculature could complement this by facilitating the entry of plasma proteins into the tumor space, permitting them to exert effects on growth and survival pathways. Plasma proteins could act directly (on the cancer cells) or indirectly (via the stroma), and could conceivably stimulate cell proliferation, enhance cell survival, promote angiogenesis, and/or provide the cells with essential nutrients. Since increased vascular permeability is a hallmark of inflammation and since chronic inflammation is a forerunner to cancer, we also suggest that the prolonged influx of plasma proteins during chronic inflammation could contribute to the carcinogenic process. Perhaps over time and in sufficient quantity, the extruded plasma proteins and the attendant edema set up a feed-forward cycle that exacerbates the inflammation and potentiates the formation of mutagens and growth regulators. It is tempting to speculate that differences in tumor growth/metastasis and patient outcome are at least partly due to the degree of permeability of the tumor vasculature.

PMID:
22459481
DOI:
10.1016/j.mehy.2012.02.021
[Indexed for MEDLINE]

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