JAM-C Promotes Lymphangiogenesis and Nodal Metastasis in Non-small Cell Lung Cancer

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2014 Mar 4

PMID 24584816

Citations 15

Authors

Songnan Hao

Yanmei Yang

Yan Liu

Shucai Yang

Geng Wang

Jianbing Xiao

Huidong Liu

Affiliations

Soon will be listed here.

Abstract

This study aims to investigate lymphatic metastasis-related genes in non-small cell lung carcinomas (NSCLC). NSCLC tissue was analyzed for expression of junctional adhesion molecule-C (JAM-C) protein. Our data revealed novel associations between JAM-C overexpression in primary tumors and lymphatic microvessel density (LMVD), lymph node metastasis, and poorer overall survival and recurrence-free survival. We used the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, in vivo and vitro. We found that JAM-C played an important role in different metastasis capacity of lymph node. JAM-C affected tumor growth, LNM, JAM-C, VEGF-C, vasculature, and ERK1/2 phosphorylation (p-ERK1/2). β1 integrin was involved in lymph node metastasis. Moreover, JAM-C knockdown in highly metastatic Anip973 decreased cell migration in scratch-wound assays. The JAM-C knockdown in Anip973 cells and JAM-C cDNA in AGZY83-a cells regulated the vascular endothelial growth factor C (VEGF-C) expression. Immunofluorescence showed that blocked VEGF-C expression in JAM-C shRNA Anip973 cells were restored after JAM-C treatment. JAM-C-induced VEGF-C in JAM-C cDNA AGZY83-a cells was also effectively inhibited by treatment with an antibody specifically against JAM-C. Use of media from Anip973 cells, AGZY83-a, and A549cells lung cancer cells that overexpressed or downregulated JAM-C was demonstrated to affect activity of VEGF-C-induced β1 integrin subunit or ERK activity in human dermal lymphatic endothelial cells (HDLEC) treated with VEGF-C or inhibitory antibody to JAM-C. Overall, these results indicate that JAM-C could mediate metastasis as it contributes to VEGF-C expression in cancer cells. JAM-C affects β1and ERK activation in HDLEC, thus promoting lymphangiogenesis and nodal metastasis. Our findings indicate that JAM-C may be a therapeutic target for preventing and treating lymphatic metastases.

Citing Articles

Triage performance of PAX1/JAM3 in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China.

Chen X, Jin X, Kong L, Liou Y, Liu P, Dong Z Clin Epigenetics. 2024; 16(1):108.

PMID: 39152491 PMC: 11330154. DOI: 10.1186/s13148-024-01731-w.

JAM3 promotes cervical cancer metastasis by activating the HIF-1α/VEGFA pathway.

Peng J, Chen Y, Yin A BMC Womens Health. 2024; 24(1):293.

PMID: 38760803 PMC: 11100123. DOI: 10.1186/s12905-024-03127-7.

Advances in lymphatic metastasis of non-small cell lung cancer.

Zhang X, Ma L, Xue M, Sun Y, Wang Z Cell Commun Signal. 2024; 22(1):201.

PMID: 38566083 PMC: 10986052. DOI: 10.1186/s12964-024-01574-1.

Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling.

Lu J, Bang H, Kim S, Cho S, Ashktorab H, Smoot D Oncogene. 2020; 40(5):922-936.

PMID: 33288885 DOI: 10.1038/s41388-020-01571-x.

Junctional Adhesion Molecules in Cancer: A Paradigm for the Diverse Functions of Cell-Cell Interactions in Tumor Progression.

Lauko A, Mu Z, Gutmann D, Naik U, Lathia J Cancer Res. 2020; 80(22):4878-4885.

PMID: 32816855 PMC: 7669553. DOI: 10.1158/0008-5472.CAN-20-1829.

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