Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Author:

Panda Venketesh K.1ORCID,Mishra Barnalee1,Nath Angitha N.1,Butti Ramesh2,Yadav Amit Singh3ORCID,Malhotra Diksha1,Khanra Sinjan1ORCID,Mahapatra Samikshya1,Mishra Priyanka1,Swain Biswajit1,Majhi Sambhunath1,Kumari Kavita1,Radharani N. N. V.3,Kundu Gopal C.14

Affiliation:

1. School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India

2. Division of Hematology and Oncology, Department of Internal Medicine, Southwestern Medical Center, University of Texas, Dallas, TX 75235, USA

3. Biomedical Centre, Faculty of Medicine, Lund University, 223 62 Lund, Sweden

4. Kalinga Institute of Medical Sciences (KIMS), KIIT Deemed to be University, Bhubaneswar 751024, India

Abstract

The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, 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 is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have 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 dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

Funder

Science and Engineering Research Board

Department of Biotechnology

DST INSPIRE Fellowship Program

Publisher

MDPI AG

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