The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

Sep 24, 2026

Uploaded by Oliver

Macrophages infiltrating the tumor microenvironment, termed tumor-associated macrophages (TAMs), drive protumor activities including invasion, metastasis, and immunosuppression; higher TAM density is linked to poor outcomes across many cancers. Phosphoprotein 1 (SPP1/osteopontin) is a multifunctional secreted phosphorylated glycoprotein whose expression correlates with worse prognosis. The review highlights SPP1 on TAMs in lung adenocarcinoma as associated with poor prognosis and chemoresistance and proposes SPP1 as a marker for monocyte-derived protumor TAM subpopulations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Introduction

Tumor Microenvironment and TAMs

SPP1/Osteopontin in Cancer

SPP1 as a Marker for Protumor TAMs

SPP1/CD44 Axis in Chemoresistance

cancers Review The Signiﬁcance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages Eri Matsubara 1,2,†, Hiromu Yano 1,†, Cheng Pan 1, Yoshihiro Komohara 1,3, *, Yukio Fujiwara 1, Shukang Zhao 1,2, Yusuke Shinchi 2, Daisuke Kurotaki 4 and Makoto Suzuki 2, * Citation: Matsubara, E.; Yano, H.; Pan, C.; Komohara, Y.; Fujiwara, Y.; Zhao, S.; Shinchi, Y.; Kurotaki, D.; Suzuki, M. The Signiﬁcance of SPP1 in Lung Cancers and Its Impact asa Marker for Protumor Tumor-Associated Macrophages. Cancers 2023, 15, 2250. [https://](https://)[ ](https://)[doi.org/10.3390/cancers15082250](doi.org/10.3390/cancers15082250) Academic Editor: Noriaki Sunaga Received: 15 March 2023 Revised: 7 April 2023 Accepted: 10 April 2023 Published: 12 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan 2 Department of Thoracic Surgery and Breast Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan 3 Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-8556, Japan 4 Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan * [Correspondence: ycomo@kumamoto-u.ac.jp](Correspondence: ycomo@kumamoto-u.ac.jp) (Y.K.); [smakoto@kumamoto-u.ac.jp](smakoto@kumamoto-u.ac.jp) (M.S.); Tel.: +81-96-373-5095 (Y.K.); +81-96-373-5533 (M.S.)† These authors contributed equally to this work. Simple Summary: Macrophages that inﬁltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs) . Phosphoprotein 1 (SPP1), also known as osteopontin, is amultifunctional secreted phosphorylated glycoprotein. In this review, we summarize the signiﬁcance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of TAMs in lung adenocarcinoma. (1) The presence of TAMs is reportedly a poor prognostic factor in lung cancer. (2) We recently revealed that SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma. (3) SPP1 is a potentially useful marker for detecting monocyte-derived TAMs. Abstract: Macrophages are a representative cell type in the tumor microenvironment. Macrophages that inﬁltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs) . TAMs exhibit protumor functions related to invasion, metastasis, and immunosuppression, and an increased density of TAMs is associated with a poor clinical course in many cancers. Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional secreted phosphorylated glycoprotein. Although SPP1 is produced in a variety of organs, at the cellular level, it is expressed on only a few cell types, such as osteoblasts, ﬁbroblasts, macrophages, dendritic cells, lymphoid cells, and mononuclear cells. SPP1 is also expressed by cancer cells, and previous studies have demonstrated correlations between levels of circulating SPP1 and/or increased SPP1 expression on tumor cells and poor prognosis in many types of cancer. We recently revealed that SPP1 expression on TAMsis correlated with poor prognosis and chemoresistance in lung adenocarcinoma. In this review, we summarize the signiﬁcance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of monocyte-derived TAMs in lung adenocarcinoma. Several studies have shown that the SPP1/CD44 axis contribute to cancer chemoresistance in solid cancers, so

FAQs

What role do tumor-associated macrophages (TAMs) play in lung cancer?

TAMs support protumor functions such as invasion, metastasis, and immunosuppression, and a higher TAM density is associated with a poor clinical course.

What is SPP1 (osteopontin) and why is it important in this review?

SPP1 is a multifunctional secreted phosphorylated glycoprotein. Its expression has been linked to poor prognosis, and the review focuses on its significance in lung cancer via TAM biology.

How is SPP1 related to chemoresistance in lung adenocarcinoma?

SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma, and the SPP1/CD44 axis is discussed as a key mechanism for cell-to-cell communication between cancer cells and TAMs.

Sep 24, 2026

Uploaded by Oliver