Abstract
Background: Tumor-associated macrophages in human breast cancer are poorly understood. Specific tumor-associated macrophage-related molecular mechanisms among different intrinsic molecular subtypes remain unclear. Here, we have identified and explored the roles of the tumor-associated macrophages novel marker: CD204 in different subtypes of breast cancer.Results: CD204 was upregulated in four subtypes of breast cancer, and this was associated with poor survival outcomes. CD204 could promote tumor cell proliferation, migration, and invasion and was involved in immune system-related pathways among all subtypes. Special pathways in each subtype were also found. High CD204 mRNA expressions were associated with high proportions of protumor immune cell populations, and most immunoinhibitors positive correlated with CD204 expression in all subtypes.Conclusions: These findings contribute to a better understanding and managing the protumor phenotype of tumor-associated macrophages in different subtypes of breast cancer.Methods: The expression of CD204 and its clinical outcome were analyzed. The roles of CD204 in the regulation of tumor cell proliferation, migration, and invasion were studied. Potential pathways influenced by CD204 were displayed. Immune cell infiltration in different CD204 mRNA expression status and correlations between CD204 and immunoinhibitors were also analyzed.
Highlights
Breast cancer is the leading invasive malignancy and the second leading cause of tumor-related mortality among females worldwide [1]
CD163, CD204 (MSR1), and CD206 (MRC1) have been used to detect tumor-associated macrophages (TAMs) in mouse models [22]. To determine how these markers are expressed in tumors in comparison with normal tissue, the mRNA levels were analyzed using The Cancer Genome Atlas (TCGA) database
Only CD204 was to be upregulated in breast cancer tissue (Figure 1A), suggesting its important role
Summary
Breast cancer is the leading invasive malignancy and the second leading cause of tumor-related mortality among females worldwide [1]. Different treatment modalities toward distinct subtypes are applied in clinical practice, there is a decrease in breast cancer mortality [4]. Specific tumorassociated macrophage-related molecular mechanisms among different intrinsic molecular subtypes remain unclear. We have identified and explored the roles of the tumor-associated macrophages novel marker: CD204 in different subtypes of breast cancer. CD204 could promote tumor cell proliferation, migration, and invasion and was involved in immune system-related pathways among all subtypes. High CD204 mRNA expressions were associated with high proportions of protumor immune cell populations, and most immunoinhibitors positive correlated with CD204 expression in all subtypes. Conclusions: These findings contribute to a better understanding and managing the protumor phenotype of tumor-associated macrophages in different subtypes of breast cancer. Immune cell infiltration in different CD204 mRNA expression status and correlations between CD204 and immunoinhibitors were analyzed
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