School of Graduate Studies, Rutgers University, Piscataway, NJ 08901, USA.
Creatv MicroTech, Inc., 9 Deer Park Dr., Monmouth Junction, NJ 08852, USA.
Int J Mol Sci. 2022 Jun 30;23(13):7299. doi: 10.3390/ijms23137299.
The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell trafficking into the circulation. Cancer-associated macrophage-like cells (CAMLs) are pro-tumor polynucleated monocytic cells of hematopoietic origin emanating from tumors which may aid in circulating tumor cell (CTC) dissemination into the circulation. We examined the linkage between Beta-2 adrenergic receptor (B2AR) signaling in CAMLs and CTCs by establishing expression profiles in a model BC cell line (MDA-MB-231). We compared the model to CAMLs and CTCs found in patents. Although internalization events were observed in patients, differences were found in the expression of B2AR between the tumor cell lines and the CAMLs found in patients. High B2AR expression on patients' CAMLs was correlated with significantly more CAMLs in the circulation ( = 0.0093), but CTCs had no numerical relationship ( = 0.1565). High B2AR CAML expression was also significantly associated with a larger size of CAMLs ( = 0.0073), as well as being significantly associated with shorter progression-free survival ( = 0.0097) and overall survival ( = 0.0265). These data suggest that B2AR expression on CAMLs is closely related to the activation, intravasation, and growth of CAMLs in the circulation.
β受体阻滞剂在乳腺癌（BC）患者中的应用与远处转移、癌症复发和癌症死亡率的降低有关。研究表明，儿茶酚胺能通路直接参与交感神经驱动的促肿瘤微环境增殖和肿瘤细胞向循环系统的转移。癌症相关巨噬细胞样细胞（CAMLs）是来源于肿瘤的促肿瘤多形核单核细胞，可能有助于循环肿瘤细胞（CTC）扩散到循环系统中。我们通过建立乳腺癌细胞系（MDA-MB-231）的表达谱来研究 CAMLs 中β-2 肾上腺素能受体（B2AR）信号与 CTCs 之间的联系。我们将该模型与患者中发现的 CAMLs 和 CTCs 进行了比较。尽管在患者中观察到内化事件，但在肿瘤细胞系和患者中发现的 CAMLs 之间，B2AR 的表达存在差异。患者 CAMLs 上的高 B2AR 表达与循环中明显更多的 CAMLs 相关（= 0.0093），但 CTCs 没有数量关系（= 0.1565）。高 B2AR CAML 表达也与 CAMLs 较大的大小显著相关（= 0.0073），并且与较短的无进展生存期（= 0.0097）和总生存期（= 0.0265）显著相关。这些数据表明，CAMLs 上的 B2AR 表达与 CAMLs 在循环中的激活、浸润和生长密切相关。
