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Posted On: 08/14/2023 6:08:16 PM
Post# of 148903
They are all excited about a new drug that can block a protein that induces cancer metastasis. Once again a drug that does one small part of what leronlimab does.
Quote:
Targeted Destruction of S100A4 Inhibits Metastasis of Triple Negative Breast Cancer Cells
Most patients who die of cancer do so from its metastasis to other organs. The calcium-binding protein S100A4 can induce cell migration/invasion and metastasis in experimental animals and is overexpressed in most human metastatic cancers. Here, we report that a novel inhibitor of S100A4 can specifically block its increase in cell migration in rat (IC50, 46 µM) and human (56 µM) triple negative breast cancer (TNBC) cells...
The lead PROTAC compound demonstrates proof of principle that specific destruction of S100A4 can dramatically reduce in vitro properties associated with metastasis, as well as inhibiting the formation and provoking the destruction of metastases in an experimental model [35,36] of TNBC in mice, suggesting that it has potential as an antimetastatic agent in humans.
https://www.mdpi.com/2218-273X/13/7/1099
Quote:
Metastasis-Inducing S100A4 and RANTES Cooperate in Promoting Tumor Progression in Mice
We found that RANTES stimulates the externalization of S100A4 via microparticle shedding from the plasma membrane of tumor and stroma cells. Conversely, the released S100A4 protein induces the upregulation of fibronectin (FN) in fibroblasts and a number of cytokines, including RANTES in tumor cells as well as stimulates cell motility in a wound healing assay. Importantly, using wild type and S100A4-deficient mouse models, we demonstrated a substantial influence of tumor cell-derived RANTES on S100A4 release into blood circulation which ultimately increases the metastatic burden in mice.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860983/
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