Abstract B019: Identify features of fibroblast and macrophage which regulate metastasis of triple-negative breast cancer

Abstract

Abstract The tumor microenvironment (TME), which the cancer is known to remodel, can interact with cancer in various ways, such as promoting or hindering metastasis. The challenge with comprehending TME is that each patient's individual variance makes it difficult to carry out a consistent analysis. We used the PDX model to analyze the alterations entirely brought about by cancer cells of each patient in the same environment exclusively. In 121 breast cancer patients, we created a PDX model and performed WES and RNA-seq. We repeatedly performed metastatic induction tests on the models of 26 TNBC patients among the PDX models we generated. The replicated experiments confirmed that cancer cells with frequent metastasis usually spread well, while cancer cells with seldom metastases rarely metastasize. For each of the five samples that had the greatest and worst rates of metastasis, the pre-metastatic xenograft tumor was analyzed using scRNA-seq. Metastasis could not be predicted by only cancer cells because there was no difference between the two groups. Still, fibroblasts and macrophages had distinct gene markers before metastasis which can predict metastasis. To explore TME that develops pre-metastatic niches (PMN) in organs that would be metastasis targets, we developed a metastatic model using 4T1 cell lines. Daily lung macrophage RNA-seq, lung WES, and lung scRNA-seq procedures were carried out for four weeks to examine the precise timing of metastasis and the daily changes in the transcriptome. Surprisingly, a few days before the presence of any cancer cells, the gene expression of lung macrophages had already undergone significant modification. Additionally, only injections of tumor-conditioned media that mimicked metastasis could activate PMN in lung macrophages. Citation Format: Woochan Lee, Hyewon Chung, Woohang Heo, Hyeong-Gon Moon, Seung Hyeok Seok, Jong-Il Kim. Identify features of fibroblast and macrophage which regulate metastasis of triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B019.