title: Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells.
abstract: Tumor hypoxia is one of the important features of lung adenocarcinoma. Chemokines might mediate the effects caused by tumor hypoxia. As confirmed in tumor tissue and serum of patients, CC chemokine 28 (CCL28) was the only hypoxia induced chemokine in lung adenocarcinoma cells. CCL28 could promote tube formation, migration and proliferation of endothelial cells. In addition, angiogenesis was promoted by CCL28 in the chick chorioallantoic membrane and matrigel implanted in dorsal back of athymic nude mice (CByJ.Cg-Foxn1(nu)/J). Tumors formed by lung adenocarcinoma cells with high expression of CCL28 grew faster and had a higher vascular density, whereas tumor formation rate of lung adenocarcinoma cells with CCL28 expression knockdown was quite low and had a lower vascular density. CCR3, receptor of CCL28, was highly expressed in vascular endothelial cells in lung adenocarcinoma when examining by immunohistochemistry. Further signaling pathways in endothelial cells, modulated by CCL28, were analyzed by Phosphorylation Antibody Array. CCL28/CCR3 signaling pathway could bypass that of VEGF/VEGFR on the levels of PI3K-Akt, p38 MAPK and PLC gamma. The effects could be neutralized by antibody against CCR3. In conclusion, CCL28, as a chemokine induced by tumor hypoxia, could promote angiogenesis in lung adenocarcinoma through targeting CCR3 on microvascular endothelial cells.
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Guichun
authors.initials: G
authors.lastname: Huang
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Medical School of Nanjing University, Nanjing, China.
authors.forename: Sunan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000818:Animals; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D054397:Receptors, CCR3 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C414047:CCL28 protein, human; C515350:CCR3 protein, human; D019742:Chemokines, CC; D054397:Receptors, CCR3