Junctional adhesion molecule-C promotes metastatic potential of HT1080 human fibrosarcoma.
The junctional adhesion molecule (JAM) family is a key molecule in a process called transendothelial migration or diapedesis. Here, we report implications of JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19 kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent metastatic properties. Especially in murine K-1735 melanoma cell lines, the highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080 fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells showed a significant increase in the adhesion to various extracellular substrates and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using small interfering RNA resulted in the suppression of both the adhesion and the invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo experimental metastatic model. The results showed that the overexpression of hJAM-C in HT1080 cells significantly decreased the life spans of the tumorbearing mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight gain of the lungs with metastatic colonies. We conclude that the expression of JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to extracellular matrices and the subsequent invasion.
Fuse
Chiaki
C
Department of Medical Biochemistry and Center of Excellence Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Ishida
Yuuki
Y
Hikita
Tomoya
T
Asai
Tomohiro
T
Oku
Naoto
N
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D003094:Collagen / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004338:Drug Combinations; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D004338:Drug Combinations; D007136:Immunoglobulins; C448000:JAM3 protein, human; C486723:Jam3 protein, mouse; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen