CD204-Positive Tumor-associated Macrophages Relate to Malignant Transformation of Colorectal Adenoma

Taniyama, Daiki; Taniyama, Kiyomi; Kuraoka, Kazuya; Yamamoto, Hideki; Zaitsu, Junichi; Saito, Akihisa; Sakamoto, Naoya; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru

doi:10.21873/anticanres.13403

Cited by 12 publications

(12 citation statements)

References 18 publications

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“…Besides, patients with CD206+ TAM density and high CD206/CD68 ratio had significantly worse DFS and OS (124). CD204+ TAMs were abundantly detected in high-grade colorectal adenomas in comparison with low-grade adenomas that was shown immunohistochemically in 88 tubular or tubulovillous adenomas (131). In advanced colorectal cancer (stage IV), patients with a high number of peritumoral or intratumoral stabilin-1+ macrophages had a shorter DSS that was found in the Finland cohort of 159 patients.…”

Section: Negative Role Of M2-like Tams In Prognosis Of Crcmentioning

confidence: 80%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth

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Section: Negative Role Of M2-like Tams In Prognosis Of Crcmentioning

confidence: 80%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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“…In CRC, TAMs possess an intricate role, as their distribution towards the tumor might increase or hinder tumor growth [ 169 ]. High numbers of CD68+ TAMs in the invasive front were associated with favorable outcome, while other reports indicated that intratumoral CD68+ TAM counts were related with tumor penetration, lymph node metastasis and advanced stages of colorectal cancer [ 173 , 174 , 175 ]. Thus, the role of TAMs and their subsets remain to be defined.…”

Section: The Role Of P53 In the Tumor Microenvironmentmentioning

confidence: 99%

“…However, p53 was found to regulate cells of the innate immune system including TAMs. Although the underlying mechanism is unclear and needs further investigation, p53 expression in tumor cells correlated with CD204+ TAMs and density of tumor vessels in CRC [ 173 ].…”

Section: The Role Of P53 In the Tumor Microenvironmentmentioning

confidence: 99%

The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy

Michel

Kaps

Maderer

et al. 2021

Cancers

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Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.

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“…TAMs in CRC patients are associated with expansion of the microvascular bed. CD204-positive TAMs are related to the malignant transformation of colorectal adenomas ( 39 ). TAMs have been indicated to be a prognostic and predictive biomarker of stage II colon cancer in patients receiving adjuvant chemotherapy ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression

Liu

et al. 2021

Front. Oncol.

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Colorectal cancer (CRC) is the third most common cancer worldwide. Here, we identified tumor-associated macrophages (TAMs) as regulators of genes in CRC. In total, the expressions of 457 genes were dysregulated after TAM coculture; specifically, 344 genes were up-regulated, and 113 genes were down-regulated. Bioinformatic analysis implied that these TAM-related genes were associated with regulation of the processes of macromolecule metabolism, apoptosis, cell death, programmed cell death, and the response to stress. To further uncover the interplay among these proteins, we constructed a PPI network; 15 key regulators were identified in CRC, including VEGFA, FN1, JUN, CDH1, MAPK8, and FOS. Among the identified genes, we focused on PSMA2 and conducted loss-of-function experiments to validate the functions of PSMA2 in CRC. To further determine the mechanism by which PSMA2 affected CRC, we conducted multiple assays in CRC cell lines and tissues. PSMA2 enhanced the proliferation, migration and invasion of CRC cells. Moreover, our data indicated that PSMA2 expression was dramatically increased in stage 1, stage 2, stage 3, and stage 4 CRC samples. Our data indicated that PSMA2 was one target of miR-132. A miR-132 mimic greatly hindered CRC cell proliferation. In addition, the luciferase assay results revealed that miR-132 directly regulated PSMA2. Moreover, our data indicated that miR-132 expression was greatly decreased in CRC samples, which was associated with longer survival times of CRC patients, implying that miR-132 was a probable biomarker for CRC. Collectively, these data indicate that PSMA2 is a promising target for the therapy of CRC.

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CD204-Positive Tumor-associated Macrophages Relate to Malignant Transformation of Colorectal Adenoma

Cited by 12 publications

References 18 publications

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy

Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression

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