Up-regulation of METCAM-MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cellsReport as inadecuate




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BMC Cancer

, 11:113

Cell and molecular biology

Abstract

BackgroundConflicting research has identified METCAM-MUC18, an integral membrane cell adhesion molecule CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells.

MethodsThree breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM-MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein.

MCF7 cells were transfected with the human METCAM-MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM-MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM-MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM-MUC18 antibody.

ResultsIn MCF7 cells, enforced METCAM-MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM-MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM-MUC18 antibody completely destroyed their growth in the 3D culture.

ConclusionThese findings support the notion that human METCAM-MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

AbbreviationsCAMcell adhesion molecule

FBSfetal bovine serum

G418-clonesG418-resistant clone

huMETCAM-MUC18human METCAM-MUC18

IHCimmunohistochemistry

METCAMmetastasis cell adhesion molecule

PBSphosphate-buffered saline. SCID mice: severe combined immune deficiency mice.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-11-113 contains supplementary material, which is available to authorized users.

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Author: Guo-fang Zeng - Shao-xi Cai - Guang-Jer Wu

Source: https://link.springer.com/



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