Metastatic colorectal cancer cells upregulate SMLR1 that interacts with tumor-associated macrophages in the liver

Chi Wut Wong; Lihua Wang; Jorge Prado Balcazar; Yong Chen; Xiling Shen

doi:10.47248/chp2401010003

Cancer Heterogeneity and Plasticity 2024;1(1):0003 | https://doi.org/10.47248/chp2401010003

Original Research Open Access

Metastatic colorectal cancer cells upregulate SMLR1 that interacts with tumor-associated macrophages in the liver

Chi Wut Wong ^{1,2,3,† ‡} , Lihua Wang ^3,† , Jorge Prado Balcazar ³ , Yong Chen ^3,4 , Xiling Shen ^1,5,‡

1. Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA
2. Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA
3. Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA
4. Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410013, China
5. Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA

‡ Current Affiliation: GI Medical Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA
† These authors contributed equally to this work.

Correspondence: Xiling Shen

Academic Editor(s): Dean Tang

Received: Mar 30, 2024 | Accepted: Jun 10, 2024 | Published: Jul 18, 2024

Cite this article: Wong C, Wang L, Balcazar J, Chen Y, Shen X. Metastatic colorectal cancer cells upregulate SMLR1 that interacts with tumor-associated macrophages in the liver. Cancer Heterog Plast 2024; 1(1):0003. https://doi.org/10.47248/chp2401010003

Abstract

Colorectal cancer liver metastasis (CRLM) is the most common form of metastatic colorectal cancer (CRC), one of the leading causes of cancer deaths. The CRLM microenvironment tends to be more immunosuppressive, making immunotherapy less effective. By transcriptomics analysis, we discovered that small leucine-rich protein 1 (SMLR1) is upregulated in CRC liver metastases compared to primary tumors. High SMLR1 expression by the cancer is associated with poor prognosis. Proteomics analysis and cell retention assay revealed associations between SMLR1 and mannose receptor C-type 1 (MRC1, CD206) and sialic acid binding Ig-like lectin 1 (SIGLEC1, CD169) expressed on tumor-associated macrophages in the metastatic liver microenvironment. These data provide evidence that cancer cells modulate their metastatic niche via the upregulation of SMLR1 and physical interaction with immunosuppressive macrophages in the liver.

Keywords

Colorectal cancer, liver metastasis, small leucine-rich protein 1 (SMLR1), tumor-associated macrophages

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