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Updated: Feb 13, 2026
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer
Huimin Lu1, Nicholas Bowler2, Larry A Harshyne3
1Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Abstract:
Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment. We show that αvβ6 is transferred from cancer cells to monocytes, including β6-null monocytes, by exosomes and that monocytes from prostate cancer patients, but not from healthy volunteers, express αvβ6. Cancer cell exosomes, purified via density gradients, promote M2 polarization, whereas αvβ6 down-regulation in exosomes inhibits M2 polarization in recipient monocytes. Also, as evaluated by our proteomic analysis, αvβ6 down-regulation causes a significant increase in donor cancer cells, and their exosomes, of two molecules that have a tumor suppressive role, STAT1 and MX1/2. Finally, using the Ptenpc-/- prostate cancer mouse model, which carries a prostate epithelial-specific Pten deletion, we demonstrate that αvβ6 inhibition in vivo causes up-regulation of STAT1 in cancer cells. Our results provide evidence of a novel mechanism that regulates M2 polarization and prostate cancer progression through transfer of αvβ6 from cancer cells to monocytes through exosomes.
Insights
Prostate cancer cells transfer the integrin αvβ6 via exosomes to monocytes, promoting tumor progression. Inhibiting αvβ6 up-regulates tumor-suppressive molecules STAT1 and MX1/2, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Prostate cancer therapies face challenges due to drug-resistant, metastatic phenotypes.
- Integrin αvβ6, an epithelial-specific surface receptor, is identified as a promising therapeutic target for prostate cancer.
- αvβ6 is present in various cancers but not in normal tissues, making it a selective target.
Purpose of the Study:
- To investigate a novel αvβ6-mediated signaling pathway impacting the tumor microenvironment in prostate cancer.
- To explore the transfer of αvβ6 from prostate cancer cells to monocytes via exosomes.
- To determine the effect of αvβ6 on monocyte polarization and tumor-suppressive molecule expression.
Main Methods:
- Purification of cancer cell exosomes using density gradients.
- Analysis of αvβ6 expression in monocytes from prostate cancer patients and healthy volunteers.
- Assessment of M2 polarization in recipient monocytes.
- Proteomic analysis of cancer cells and exosomes.
- In vivo studies using the Ptenpc-/- prostate cancer mouse model.
Main Results:
- αvβ6 is transferred from cancer cells to monocytes via exosomes, including in β6-null monocytes.
- Monocytes from prostate cancer patients express αvβ6, unlike those from healthy individuals.
- Cancer cell exosomes promote M2 polarization; αvβ6 down-regulation inhibits this effect.
- αvβ6 down-regulation increases tumor-suppressive molecules STAT1 and MX1/2 in cancer cells and their exosomes.
- In vivo αvβ6 inhibition up-regulates STAT1 in cancer cells.
Conclusions:
- A novel mechanism involving exosomal transfer of αvβ6 from cancer cells to monocytes regulates M2 polarization and prostate cancer progression.
- Targeting αvβ6 may offer a new therapeutic strategy by modulating the tumor microenvironment and enhancing tumor suppression.
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