Periostin in Malignant Peripheral Nerve Sheath Tumors (MPNST): Insights into Its Functions and Therapeutic Potential

Authors

• V Verdi
• C Cero
• BR Wei
• HR Shive

Abstract

Periostin (POSTN), a secreted extracellular matrix protein, plays a key multifaceted role in cancer biology through its involvement in tumor progression, metastasis, and the tumor microenvironment modulation. Secreted POSTN facilitates tumor cell proliferation, survival, and migration by interacting with Integrins in an autocrine or paracrine fashion, resulting in activation of downstream signaling such as the PI3K/Akt and MAPK pathways. Although the roles of POSTN in modulating the tumor microenvironment are not fully understood, it is known to induce fibrotic stroma development and influence immune cell infiltration in various types of human cancer, thus affecting tumor progression and therapy response. POSTN inhibition is being explored as a novel strategy to disrupt tumor growth and metastases. We have identified POSTN as a candidate mediator of cancer progression in malignant peripheral nerve sheath tumors (MPNSTs), a rare type of soft tissue sarcoma with poor prognosis and limited treatment options. In this study we show how silencing POSTN expression through RNA interference leads to significant phenotypic alterations in three MPNST tumor cell lines, such as changes in Integrin receptor expression and cytosolic volume. Moreover, POSTN knockdown induces significant growth impairment and reduced viability in MPNST cells. Our findings provide grounds for further research into POSTN-mediated functions in MPNST tumor pathogenesis and tumor microenvironment and may pave the way for future POSTN-targeted therapies for MPNST patients.

Scientific Focus Area: Cancer Biology

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