Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers

作者：Mori Taizo; Kariya Yoshinobu; Komiya Eriko; Higashi Shouichi; Miyagi Yohei; Sekiguchi Kiyotoshi; Miyazaki Kaoru^*

来源：Cancer Science, 2011, 102(5): 1095-1100.

DOI：10.1111/j.1349-7006.2011.01892.x

Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the alpha 4 (laminin-411/421) and alpha 5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the alpha 3B, beta 1 and gamma 1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin alpha 3B chain in normal mammary glands and breast cancers, in comparison with the alpha 4 and alpha 5 laminins. In the immunohistochemical analysis, the alpha 3B laminin was co-localized with the alpha 4 and alpha 5 laminins in the BM of venules and capillaries of normal breast tissues, but alpha 3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the alpha 4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The alpha 5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-alpha significantly suppressed the laminin alpha 3B expression in vascular endothelial cells, while it, as well as IL-1 beta and TGF-alpha, upregulated the alpha 4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis. (Cancer Sci 2011; 102: 1095-1100).

• 出版日期2011-5