Language
English
Publication Date
7-23-2024
Journal
Cell Reports
DOI
10.1016/j.celrep.2024.114377
PMID
38889005
PMCID
PMC11380445
PubMedCentral® Posted Date
9-7-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells. Cx43-M2 significantly decreases breast cancer metastasis, osteosarcoma growth, and osteolytic activity, while improving survival rates in mice. The antibody's inhibition of breast cancer and osteosarcoma is dose dependent in both mouse and human cancer metastatic models. Furthermore, Cx43-M2 enhances anti-tumor immunity by increasing the population and activation of tumor-infiltrating immune-promoting effector T lymphocytes, while reducing immune-suppressive regulatory T cells. Our results suggest that the Cx43-M2 antibody, by activating Cx43 hemichannels and facilitating ATP release and purinergic signaling, transforms the cancer microenvironment from a supportive to a suppressive state. Collectively, our study underscores the potential of Cx43-M2 as a therapeutic for treating breast cancer bone metastasis and osteosarcoma.
Keywords
Osteosarcoma, Animals, Osteocytes, Adenosine Triphosphate, Humans, Female, Breast Neoplasms, Connexin 43, Mice, Bone Neoplasms, Cell Line, Tumor, Tumor Microenvironment, Antibodies
Published Open-Access
yes
Recommended Citation
Riquelme, Manuel A; Wang, Xuewei; Acosta, Francisca M; et al., "Antibody-Activation of Connexin Hemichannels in Bone Osteocytes With ATP Release Suppresses Breast Cancer and Osteosarcoma Malignancy" (2024). The Brown Foundation: Institute of Molecular Medicine. 6.
https://digitalcommons.library.tmc.edu/molecular_med/6
Graphical Abstract