2. Academic Validation
  3. Prognosis of Midkine and AT1R expression in resectable head and neck squamous cell carcinoma

Prognosis of Midkine and AT1R expression in resectable head and neck squamous cell carcinoma

  • Cancer Cell Int. 2023 Sep 24;23(1):212. doi: 10.1186/s12935-023-03060-z.
Tai-Jan Chiu 1,  Chang-Han Chen 2,  Yi-Ju Chen 3,  Yinshen Wee 4,  Ching-Shuen Wang 5,  Sheng-Dean Luo 6 7 8
Affiliations

Affiliations

  • 1 Department of Hematology‑Oncology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan.
  • 2 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 3 Kaohsiung Cancer Prevention and Screening Center, Kaohsiung, 833, Taiwan.
  • 4 Department of Pathology, University of Utah, Salt Lake City, UT, 84112, USA.
  • 5 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, 110, Taiwan.
  • 6 Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan. rsd0323.tw@gmail.com.
  • 7 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. rsd0323.tw@gmail.com.
  • 8 School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, 33302, Taiwan. rsd0323.tw@gmail.com.
PMID: 37743493 DOI: 10.1186/s12935-023-03060-z
Abstract

Background: Research studies have demonstrated that Midkine (MDK) can influence the expression and activity of Renin-angiotensin system (Ras) components. Angiotensin II is involved in tumor growth and angiogenesis in different cancers. We previously observed Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with oral cancers. These findings have prompted us to investigate whether MDK can influence the Ras pathway, mainly through its association with angiotensin II type 1 receptor (AT1R), which contributes to the observed poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients.

Methods: MDK and AT1R expressions were examined in 150 HNSCC patients post-operation by immunohistochemical staining between 1 January 2010 and 31 December 2016. We tested the over-expression and silencing of MDK to evaluate the AT1R expression and functional biological assays in HNSCC cell lines HSC-3 and SAS.

Results: Positive expression of MDK is correlated with positive AT1R expression. MDK predicted poor NSCC patients' survival. Silencing MDK could suppress AT1R and pAKT expression and reduce the growth, migration, and invasion of HNSCC cells. ARB also inhibits MDK stimulating HNSCC cell proliferation. Overexpression of MDK could upregulate AT1R and pAKT.

Conclusions: MDK is an independent prognostic factor of HNSCC post-operation, and AT1R regulates HNSCC cell growth, invasion, and migration. Positive MDK and AT1R expressions are highly correlated. Mechanistically, the interaction between MDK and AT1R is crucial for MDK-mediated cell viability, and inhibiting AT1R can effectively counteract or abolish these effects. Furthermore, MDK exerts a regulatory role in the expression of AT1R, as well as in the growth and motility of HNSCC cells. These findings highlight the involvement of the interaction between MDK, AT1R, and the pAkt signaling pathways in HNSCC cell viability growth.

Figures
Products