Premium
Fractones: tumor matrix in colon cancer, stomach cancer and glioblastoma
Author(s) -
Mercier Frederic,
Uguen Arnaud,
Marcorelles Pascale,
Fronville Alexandra,
CORCOS Laurent
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.677.14
Subject(s) - basement membrane , extracellular matrix , laminin , microbiology and biotechnology , biology , stem cell , pathology , perlecan , cancer cell , chemistry , cancer , proteoglycan , medicine , genetics
The basic pathological mechanisms leading to dysplasia, tumor progression and the destruction of adjacent tissues are not well known. Basement membranes and underlying connective tissue are part of the construction machinery that operates to form structures during development and throughout adult life. In cancer, basement membranes tend to restructure the tissue in conjunction with altered stem cells and their microenvironment‐specific extracellular niche. We have characterized a new type of extracellular matrix that we have named fractones. Fractones are chemically similar to basement membranes and consist at least of laminin isoforms, collagen‐IV, nidogen and heparan sulfate proteoglycan. However, fractones and basement membranes differ with respect to their location. Fractones reside in the parenchyma of tissues and organs and are visualized as particles by light microscopy whereas they often display a fractal ultrastructure (a reference to their name). In contrast, basement membranes form sheaths at the connective tissue/parenchyma interface and in between the layers of the vascular wall. We have shown that fractone‐associated heparan sulfates bind, concentrate and activate the FGF‐2, BMP‐4 and BMP‐7 growth factors to regulate stem cell proliferation in the neurogenic zone of the adult brain. Here, we hypothesized that fractones are produced by cancer stem cells and by their immediate progeny to bind and concentrate growth factors to their vicinity. This would participate in rerouting the activity of the physiological stem cell niche and benefit from neovascularization to capture essential nutrients and reach independence. Using immunohistochemistry for laminin, a marker of fractones and basement membranes, on sane and cancerous tissues, we have identified deficient basement membranes and a high expression of fractones in zones without basement membranes in colon cancer. In addition, a high ectopic expression of fractones was correlated with a significant decrease in vasculature in multiform glioblastoma. Our results show that fractones are associated with cancer‐specific morphological alterations. We anticipate that the alteration in binding of growth factors in cancer tissues could ultimately lead to increased proliferation coupled with a distorted neoangiogenesis. These results provide novel insights into hitherto unrevealed mechanisms, on which innovative future therapies may be based, for example using glycan antagonists of those expressed in tumor‐specific fractones. Support or Funding Information Canceropole Grand Ouest, France This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .