{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:53:43Z","timestamp":1790272423117,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:00:00Z","timestamp":1541980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Masonic Cancer Center"},{"DOI":"10.13039\/100013664","name":"College of Veterinary Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013664","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Although members of the hyaluronan (HA)\u2010CD44\/HA\u2010mediated motility receptor (RHAMM) signaling pathway have been shown to be overexpressed in lung cancer, their role in lung tumorigenesis is unclear. In the present study, we first determined levels of HA and its receptors CD44 and RHAMM in human non\u2010small cell lung cancer (NSCLC) cells and stromal cells as well as mouse lung tumors. Subsequently, we examined the role of HA\u2010CD44\/RHAMM signaling pathway in mediating the proliferation and survival of NSCLC cells and the cross\u2010talk between NSCLC cells and normal human lung fibroblasts (NHLFs)\/lung cancer\u2010associated fibroblasts (LCAFs). The highest levels of HA and CD44 were observed in NHLFs\/LCAFs followed by NSCLC cells, whereas THP\u20101 monocytes\/macrophages showed negligible levels of both HA and CD44. Simultaneous silencing of HA synthase 2 (HAS2) and HAS3 or CD44 and RHAMM suppressed cell proliferation and survival as well as the EGFR\/AKT\/ERK signaling pathway. Exogenous HA partially rescued the defect in cell proliferation and survival. Moreover, conditioned media (CM) generated by NHLFs\/LCAFs enhanced the proliferation of NSCLC cells in a HA\u2010dependent manner as treatment of NHLFs and LCAFs with HAS2 siRNA, 4\u2010methylumbelliferone, an inhibitor of HASs, LY2228820, an inhibitor of p38MAPK, or treatment of A549 cells with CD44 blocking antibody suppressed the effects of the CM. Upon incubation in CM generated by A549 cells or THP\u20101 macrophages, NHLFs\/LCAFs secreted higher concentrations of HA. Overall, our findings indicate that targeting the HA\u2010CD44\/RHAMM signaling pathway could be a promising approach for the prevention and therapy of lung cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22930","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T09:02:24Z","timestamp":1540544544000},"page":"321-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Hyaluronan\u2010CD44\/RHAMM interaction\u2010dependent cell proliferation and survival in lung cancer cells"],"prefix":"10.1002","volume":"58","author":[{"given":"Jung Min","family":"Song","sequence":"first","affiliation":[{"name":"Masonic Cancer Center University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintaek","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Minnesota Minneapolis 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