Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity

Biochemical and Biophysical Research Communications
Suguru ItoAtsushi Ochiai

Abstract

There is growing evidence that stromal fibroblasts can promote tumor progression via several mechanisms. We previously reported that podoplanin (PDPN) expressed on stromal fibroblasts is functionally protein responsible for the promotion of tumor formation in mouse subcutaneous tissue. The purpose of the present study was to reveal the molecular mechanism by which PDPN on stromal fibroblasts promotes tumor formation. The subcutaneous co-injection of the human lung adenocarcinoma cell line A549 and human fibroblasts (hFbs) overexpressing wild-type podoplanin (WT-PDPN) promoted subcutaneous tumor formation, compared with the co-injection of A549 and control hFbs (64% vs 21%). On the other hand, hFbs expressing PDPN mutant in which the cytoplasmic domain of PDPN was deleted (PDPN-Del.IC), resulted in a relatively lower level of tumor formation (33%). Since PDPN reportedly regulates RhoA activity through its cytoplasmic domain, we measured the activation state of RhoA in hFbs expressing WT-PDPN. RhoA activity was 2.7-fold higher in WT-PDPN expressing hFbs than in control hFbs. Furthermore, the subcutaneous co-injection of hFbs expressing constitutive active RhoA (G14VRhoA) and A549 cells enhanced tumor formation compared with the c...Continue Reading

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Citations

Apr 17, 2014·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·G JomrichS F Schoppmann
Aug 15, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Harumi InoueKaoru Kusama
Sep 10, 2013·Journal of Cancer Research and Clinical Oncology·Akiko TakahashiAtsushi Ochiai
Sep 17, 2015·Journal of Cancer Research and Clinical Oncology·Shinya NeriGenichiro Ishii
Dec 30, 2015·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Koichi SaruwatariGenichiro Ishii
Feb 5, 2015·International Journal of Cancer. Journal International Du Cancer·Shinya NeriAtsushi Ochiai
Jun 27, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Niharika SwainShilpa Patel
Oct 12, 2014·Journal of Cancer Research and Clinical Oncology·Shigeki SuzukiAtsushi Ochiai
Aug 17, 2016·Clinica Chimica Acta; International Journal of Clinical Chemistry·Jingwen WangJianwu Tang
Feb 10, 2019·International Journal of Molecular Sciences·Miguel QuintanillaEster Martín-Villar
Jun 20, 2020·American Journal of Rhinology & Allergy·Huan WangDehui Wang
Apr 17, 2013·International Journal of Oncology·Bartosz PulaMarzena Podhorska-Okolow
Oct 11, 2017·Molecular Medicine Reports·Guanhua ChenChunxiao Dong
Mar 27, 2013·The Journal of Biological Chemistry·Harini KrishnanGary S Goldberg
Nov 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tatsuya YoshidaAtsushi Ochiai
Jan 12, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jun SuzukiGenichiro Ishii
May 26, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Jennifer Alexander, Edna Cukierman

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