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Ectopic expression of MCAM/MUC18 increases in vitro motility and invasiveness, but decreases in vivo tumorigenesis and metastasis of a mouse melanoma K1735-9 subline in a syngeneic mouse model

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Abstract

Ectopic expression of MCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, induces two moMCAM/MUC18-minus, non-metastatic mouse melanoma K1735 sublines, K3 (tumor+/metlow) and K10 (tumor−/metlow), to metastasize to lungs in a syngeneic C3H mouse model. In this report, we extended investigation of effects of moMCAM/MUC18 expression on tumorigenesis and metastasis in another lowly metastatic, however highly tumorigenic moMCAM/MUC18-minus mouse melanoma K1735 subline, K9 (tumor+++/metlow). We transfected this subline with the moMCAM/MUC18 cDNA, selected for G418-resistant clones with different expression levels of moMCAM/MUC18, and used them for testing effects of MCAM/MUC18 expression on in vitro growth rate, motility, and invasiveness, in vivo subcutaneous tumor growth, and pulmonary metastasis in syngeneic C3H brown mice. Similar to K3 and K10 cells, increased expression of MCAM/MUC18 in K9 cells did not significantly affect in vitro growth rate, but increased in vitro motility and invasiveness. Surprisingly, increased expression of MCAM/MUC18 in K9 cells decreased their induction of tumorigenesis and suppressed their establishment of pulmonary nodules in syngeneic C3H brown mice. We concluded that increased MCAM/MUC18 expression in K9 subline increased in vitro epithelial-to-mesenchymal transition; however, it suppressed in vivo tumorigenicity and metastasis. Thus MCAM/MUC18 acts as a tumor and metastasis suppressor for the K9 subline, different from its role in other K1735 sublines, K3 and K10. Different intrinsic co-factors in different K1735 sublines, which modulate the functions of MCAM/MUC18 in the cells that interact differently to the tumor microenvironment, may render sublines manifest differently in tumorigenicity and metastasis in vivo.

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Abbreviations

CAM:

Cell adhesion molecule

FBS:

Fetal bovine serum

huMCAM/MUC18:

Human MelCAM/MUC18

Ig-like:

Immunoglobulin-like

K9:

Mouse melanoma K1735 subline #9

moMCAM/MUC18:

mouse MelCAM/MUC18

IV injection:

Intravenous injection

SC injection:

Subcutaneous injection

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Acknowledgments

I thank Qiong Peng, Pingping Fu and Mei-Whey H. Wu for technical help. This was partly supported by the funds of Emory University Research committee and Emory University Skin disease Research Center and by grants from National Science council), Taiwan (NSC-101-2320-B-033-001 and -003) (GJWu).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Guang-Jer Wu

  2. Department of Bioscience Technology and Center for Biomedical Technology, Chung Yuan Christian University, Chung Li, 32023, Taiwan

    Guang-Jer Wu

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Correspondence to Guang-Jer Wu.

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Wu, GJ. Ectopic expression of MCAM/MUC18 increases in vitro motility and invasiveness, but decreases in vivo tumorigenesis and metastasis of a mouse melanoma K1735-9 subline in a syngeneic mouse model. Clin Exp Metastasis 33, 817–828 (2016). https://doi.org/10.1007/s10585-016-9812-z

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  • DOI: https://doi.org/10.1007/s10585-016-9812-z

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