Interaction of cancer cells with platelets mediated by Necl-5/poliovirus receptor enhances cancer cell metastasis to the lungs.
Necl-5 is an immunoglobulin (Ig)-like molecule that was originally identified as a poliovirus receptor and is often upregulated in cancer cells. We recently found that it colocalizes with integrin alpha(v)beta(3) at the leading edges of moving cells and enhances growth factor-induced cell movement and proliferation. Upon cell-cell contact, Necl-5 is removed from the cell surface by its trans-interaction with the cell adhesion molecule nectin-3, resulting in reduced cell movement and proliferation. Here, we investigated the role of Necl-5 in the interaction of cancer cells with platelets. Necl-5 was upregulated in CT26 cells, a colon adenocarcinoma cell line. When CT26 cells were injected into the tail vein of mice, they were arrested in the pulmonary vessels by adhering to platelets and subsequently metastasized to the lungs. Overexpression of Necl-5 in CT26 cells enhanced this metastasis, while inhibition of the trans-interaction of Necl-5 with CD226 by an anti-Necl-5 monoclonal antibody reduced the metastasis. Depletion of platelets by treatment with a rabbit anti-mouse platelet serum reduced the Necl-5-enhanced metastasis in mice. Thus, the trans-interaction of upregulated Necl-5 in cancer cells with its counter-receptor in platelets, probably CD226, is critical for efficient metastasis of cancer cells to the lungs.
Morimoto
K
K
1KAN Research Institute Inc., Kobe MI R&D Center, Kobe, Hyogo, Japan.
Satoh-Yamaguchi
K
K
Hamaguchi
A
A
Inoue
Y
Y
Takeuchi
M
M
Okada
M
M
Ikeda
W
W
Takai
Y
Y
Imai
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor