Transitional cell carcinoma matrix stiffness regulates the osteopontin and YAP expression in recurrent patients

Hadi Ghasemi , Seyed Habibollah Mousavibahar , Mohammad Hashemnia , Jamshid Karimi , Iraj Khodadadi , Heidar Tavilani

  • Affiliations

    • 1Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
    • 2Urology & Nephrology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
    • 3Department of Pathobiology, Veterinary Medicine Faculty, Razi University, Kermanshah, Iran.
    • 4Urology & Nephrology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. tavilani@gmail.com.
    • PMID: 34086159

Abstract

Cells translate the mechanosensing of extracellular matrix component dysregulation and stiffness into the signal transduction including Osteopontin (OPN) through the Hippo pathway. But how extracellular matrix (ECM) component dysregulation and stiffness are ultimately linked to transitional cell carcinoma (TCC) development remains poorly understood. This study was aimed to evaluate the possible links between ECM component alteration after cancer surgery and OPN and Yes-associated protein (YAP) expression in TCC and adjacent tissues. In this study, we used 50 TCC (25 newly diagnosed and 25 recurrent) and 50 adjacent tissues to determine the tissue stiffness using atomic force microscopy. The mRNA expression of SPP1, Indian hedgehog (IHH), and YAP was also determined using qRT-PCR. Western blotting and ELISA were performed to assess the tissue and serum levels of OPN, respectively. To assess the glycoproteins and elastic fibers content, Periodic Acid Schiff, and Verhoeff-Van Gieson Staining were performed, respectively. Matrix stiffness was markedly higher in TCCs than adjacent tissues (p < 0.05). Gene expression analysis showed that YAP, SPP1, and IHH genes were upregulated in TCC tissues (p < 0.05). Additionally, the OPN protein overexpression was observed in the tissue and the serum of TCC patients (p < 0.05). We also found that glycoproteins, elastic fibers content of recurrent TCC tissues was remarkably higher as compared to adjacent tissues (p < 0.05). Our results suggest that glycoproteins and elastic fibers content modulation and ECM stiffness may upregulates the expression of YAP, SPP1 and IHH genes, and possibly contribute to the TCC development and relapse.

Keywords: Cancer; Indian hedgehog (IHH); Osteopontin (OPN); Tissue stiffness; Transitional cell carcinoma (TCC); Yes-associated protein (YAP).