Oral Squamous Cell Carcinoma-Derived ANGPTL3 Induces Cancer Associated Fibroblastic Phenotypes in Surrounding Fibroblasts

Document Type : Research Articles


1 Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06230, Republic of Korea.

2 Department of Dental Hygiene, Daejeon health institute of technology, Daejeon, 34504, Republic of Korea.

3 Precision Medicine Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.


Objective: Angiopoietin-like proteins (ANGPTLs) have emerged as both important regulator of lipid and glucose metabolism as well as insulin sensitivity. In particular, ANGPTL3 activity is one of the most important factors in cancer growth and invasion. Although ANGPTL3 have been studied in OSCC, but the role of ANGPTL3 between OSCC and CAFs has yet to be clearly defined. Thus, this study aimed to investigate the roles of ANGPTL3 in the differentiation of CAFs. Methods: For our study, we used hTERT-hNOFs to replace CAFs by coculturing them with oral squamous cell carcinoma (OSCC) cells. We did a microarray dataset analysis to investigate what factors secreted from OSCC cells can induce cancer associated fibroblastic phenotype in surrounding fibroblasts. The secreted factors were confirmed by RT-PCR, real-time PCR, and Western blot. Result: ANGPTL3 has the most secreted factor derived from various oral cancer cells. To investigate the role of ANGPTL3 in CAFs, we treated rhANGPTL3 in hTERT-hNOFs. The fibroblasts showed an increase of tumor-promoting cytokines (IL-6 and IL-8) and myofibroblastic markers, such as α-SMA and FAP. Conclusion: In conclusion, our study reports the first evidence that ANGPTL3 plays a crucial role in tumor microenvironments by inducing CAF. Therefore, targeting ANGPTL3 may be promising treatment strategy for CAF-targeted therapy in CAF-rich tumors. 


Main Subjects

Volume 23, Issue 12
December 2022
Pages 4315-4322
  • Receive Date: 11 August 2022
  • Revise Date: 09 October 2022
  • Accept Date: 20 December 2022
  • First Publish Date: 20 December 2022