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Biology subjects

Maeshima, Y.

Publications and source records attributed to Maeshima, Y..

2 recordsLinked to original sources

Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we report that metastasized breast cancer cells selectively eliminate CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, from the lymph nodes. The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ macrophages was reduced in metastatic lymph nodes, whereas the numbers of other major immune cell types were unaltered. We also detected the infiltration of CD169+ macrophages into metastasized cancer tissues depending on sections, suggesting that CD169+ macrophages were gradually eliminated after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging. Collectively, we propose that metastasized breast cancer cells dispel CD169+ macrophages from lymph nodes in a phased manner, disabling a critical step of anti-cancer immunity.

cancer biology↗

Senescence triggers intracellular acidification and lysosomal alkalinization via ATP6AP2 attenuation in breast cancer cells

Several chemotherapy drugs induce the senescence of cancer cells; however, the mechanism underlying intracellular pH dysregulation in senescent cells remains unclear. Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2) plays a critical role in maintaining pH homeostasis in cellular compartments. We here report a new function of ATP6AP2 in senescent breast cancer cells induced by doxorubicin and abemaciclib treatment. ATP6AP2 expression was significantly downregulated in senescent cells, leading to aberrant pH levels that impaired lysosome function and caused immune response changes. The drugs caused cell cycle arrest and proliferation suppression through the upregulation of senescence-related genes. Additionally, senescent cells showed altered inflammatory and immune transcriptional profiles by reprogramming the senescence-associated secretory phenotype. These findings suggest that ATP6AP2-mediated pH regulation during therapy-induced senescence may be linked to immune changes in senescent cancer cells. These findings provide novel insights into understanding the cellular mechanisms underlying the response to anti-cancer drugs.

cancer biology↗