Background: Tumor-associated macrophages (TAMs) are important contributors to tumor progression and metastasis. Therefore, the identification of molecules that mediate these cells’ tumor-promoting functions is highly warranted. VSIG4 has been proposed as a macrophage immune checkpoint. Hence, we aim to investigate this marker in preclinical models. Methods: Publicly available scRNAseq datasets of human colorectal (CRC) and triple-negative breast (TNBC) carcinomas and their murine counterparts were reanalyzed to investigate the expression of VSIG4 in the different TAM populations. Moreover, tumors were grown inVsig4-deficient mice to evaluate the effect on primary tumor characteristics. Finally, since liver Kupffer cells and large peritoneal macrophages are at least partly VSIG4-high, and are implicated in metastasis to those organs, the dissemination of CRC cancer cells to those sites was assessed in theVsig4-deficient mice. Results: We demonstrate thatVSIG4expression in human CRC and TNBC is mostly restricted to TAMs, and that its expression correlates with a worse prognosis. However, a striking finding was that noVsig4mRNA nor protein could be detected in the microenvironment of primary CRC and TNBC murine tumors, resulting in a similar tumor growth in wild type versusVsig4-deficient mice. Moreover, no major differences were observed in metastatic tumor load in the liver and peritoneal cavity, apart from a reduced metastasis to the omentum inVsig4-deficient animals. Conclusions: Murine cancer models are not suitable to investigate the role of VSIG4 in primary tumors and VSIG4 deficiency did not alter liver nor peritoneal cavity metastasis in murine models, with the exception of the omentum.
背景：肿瘤相关巨噬细胞（TAMs）是促进肿瘤进展和转移的重要因素。因此，识别介导这些细胞促瘤功能的分子具有重要意义。VSIG4被认为是一种巨噬细胞免疫检查点。因此，我们旨在临床前模型中研究这一标志物。 方法：重新分析公开的人类结直肠癌（CRC）和三阴性乳腺癌（TNBC）及其小鼠模型的单细胞RNA测序数据集，以研究VSIG4在不同TAM群体中的表达。此外，在Vsig4缺陷小鼠中培养肿瘤，以评估其对原发肿瘤特征的影响。最后，鉴于肝脏库普弗细胞和大腹膜巨噬细胞至少部分高表达VSIG4，并且与肿瘤向这些器官的转移有关，我们在Vsig4缺陷小鼠中评估了CRC癌细胞向这些部位的扩散情况。 结果：我们证明，VSIG4在人类CRC和TNBC中的表达主要局限于TAMs，并且其表达与较差的预后相关。然而，一个引人注目的发现是，在小鼠CRC和TNBC原发肿瘤的微环境中无法检测到Vsig4 mRNA或蛋白，导致野生型小鼠与Vsig4缺陷小鼠的肿瘤生长相似。此外，除了Vsig4缺陷动物的大网膜转移减少外，肝脏和腹膜腔的转移瘤负荷未观察到显著差异。 结论：小鼠癌症模型不适合研究VSIG4在原发肿瘤中的作用，并且在小鼠模型中，VSIG4缺陷并未改变肝脏或腹膜腔的转移，但大网膜转移除外。
VSIG4 Is Dispensable for Tumor Growth and Metastasis in Murine Colorectal and Breast Cancer Models
肿瘤(癌症)患者之家