Plasma Fibronectin Promotes Lung Metastasis by Contributions to Fibrin Clots and Tumor Cell Invasion

The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multi...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2010-06, Vol.70 (11), p.4327-4334
Main Authors: MALIK, Gunjan, KNOWLES, Lynn M, DHIR, Rajiv, SHUPING XU, SHUTING YANG, RUOSLAHTI, Erkki, PILCH, Jan
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Blood Coagulation - physiology
Carcinoma, Lewis Lung - blood
Carcinoma, Lewis Lung - pathology
Carcinoma, Lewis Lung - secondary
Cell Adhesion - physiology
Fibrin - metabolism
Fibronectins - blood
Integrin alphaVbeta3 - blood
Lung Neoplasms - blood
Lung Neoplasms - secondary
Medical sciences
Melanoma, Experimental - blood
Melanoma, Experimental - pathology
Melanoma, Experimental - secondary
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Invasiveness
Pharmacology. Drug treatments
Pneumology
Tumors
Tumors of the respiratory system and mediastinum
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Summary:The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating plasma fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin alphavbeta3. In vitro studies showed that fibrin-fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-fibronectin complexes to induce the activation of integrin alphavbeta3. Our findings reveal an important contribution of plasma fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a fibronectin-alphavbeta3 integrin axis, in which plasma fibronectin has to be incorporated into the blood clot.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-09-3312