Abstract P6-06-18: Promyelocytic leukemia (PML) is induced by tumor-associated macrophages (TAMs) in breast cancer

Abstract

Abstract Introduction: Tumor-associated macrophages (TAMs) are pivotal orchestrators of the tumor microenvironment. Clinical evidences show that density of TAMs increases with lymph node metastasis, which is associated with poor prognosis in breast cancer patients. The underlying mechanism has not been clearly elucidated. Methods: Transcriptome of MCF-7 cells cocultured with TAMs or monocyte-derived macrophages (MDMs) was analyzed and compared by RNA-seq analysis, which showed that the promyelocytic leukemia (PML) gene was significantly upregulated by TAMs (P<0.001). The upregulation of PML was further verified by qRT-PCR and immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 294 cases of breast cancer tissue with duplicate cores and 28 cases of normal breast tissue with single core. The age, sex, pathological type, histologic grade and stage of the patients were well recorded. Results: RNA-seq analysis revealed that TAMs significantly upregulated PML expression, which was confirmed by qRT-PCR. Further, the protein level of PML was detected by IHC in TMAs. As expected, 57 cores of benign breast tissue, including normal breast tissue, adjacent normal breast tissue, adenosis and fibrous tissue in invasive ductal carcinoma (IDC) and lobular carcinoma in situ (LCIS), showed absent (80.70%) or low (19.30%) staining scores. In 508 (99.03%) cores of invasive breast cancer tissue, PML expression was positively correlated with lymph node metastasis (P= 0.003). However, no significant associations were observed between PML expression and tumor stage, primary tumor size, histologic tumor grade in IDC, or PML cellular localization. Conclusion:Recently, PML, upregulated in a subset of breast cancer, has been identified as a breast cancer oncogene. Here, we demonstrated PML expression was induced by TAMs and positively correlated with lymph node metastasis. Thus, we conclude PML mediates TAMs function in breast tumorigenesis and TAMs stimulates the expression of PML in breast cancer. Citation Format: Meijun Long, Mei Yang, Jun An, Renbin Liu. Promyelocytic leukemia (PML) is induced by tumor-associated macrophages (TAMs) in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-18.