Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Venketesh K. Panda; Barnalee Mishra; Angitha N Nath; Ramesh Butti; Amit Singh Yadav; Diksha Malhotra; Sinjan Khanra; Samikshya Mahapatra; Priyanka Mishra; Biswajit Swain; Sambhunath Majhi; Kavita Kumari; NNV Radharani; Gopal C. Kundu

doi:10.20944/preprints202405.0835.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 13 May 2024 / Approved: 13 May 2024 / Online: 13 May 2024 (10:40:26 CEST)

Tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cell, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs are crucial for enhancing the treatment outcome and reducing the burden of toxicity. In this review, we provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we have dissected the signalling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancement in role of various splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSCs enhancement, immunomodulation, metastasis, chemoresistance, metabolic reprogramming and further suggest that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

breast cancer; osteopontin (OPN); tumor associated macrophages; cancer associated fibroblast; immune modulation

Biology and Life Sciences, Life Sciences

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Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

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