Prostate cancer metastasis, insulin and IL-17
Prostate cancer risk factors include high levels of insulin and chronic inflammation. An insightful study just published in the journal Prostate reveals an additional mechanism by which they promote prostate cancer metastasis. The authors state:
"Extravasation is a critical step in cancer metastasis, in which adhesion of intravascular cancer cells to the vascular endothelial cells is controlled by cell surface adhesion molecules. The role of interleukin-17 (IL-17), insulin, and insulin-like growth factor 1 (IGF1) in adhesion of prostate cancer cells to the vascular endothelial cells is unknown, which is the subject of the present study."
They analyzed human umbilical vein endothelial cells (HUVECs) and human prostate cancer cell lines (PC-3, DU-145, LNCaP, and C4–2B) for expression of vascular cell adhesion molecule 1 (VCAM-1), integrins, and cluster of differentiation 44 (CD44) to observe the effects of IL-17, insulin, and IGF1 on VCAM-1 expression and adhesion of prostate cancer cells to HUVECs.
IL-17 and autoimmunity
Practitioners should bear in mind that IL-17 is a key player in autoimmune inflammation, and that diffuse inflammatory phenomena that appear long before evolving into a well-differentiated diagnosis of specific autoimmune disease. This phenomenon appears to now be clinically ubiquitous and a factor in most complex chronic disorders. Insulin, of course, is in excess a well-known tumor promoter.
IL-17 and insulin together significantly promote prostate cancer metastasis
The authors' data reveals that IL-17 and insulin help prostate cancer cells stick the lining of blood vessels, an important step in metastasis:
"Insulin and IGF1 acted with IL-17 to increase VCAM-1 expression in HUVECs...When HUVECs were treated with IL-17, insulin or IGF1, particularly with a combination of IL-17 and insulin (or IGF1), adhesion of PC-3 and DU-145 cells to HUVECs was significantly increased. In contrast, adhesion of LNCaP and C4–2B cells to HUVECs was not affected by treatment of HUVECs with IL-17 and/or insulin/IGF1."
This revelation reminds clinicians to be attentive to the hazardous combination of chronic IL-17 mediated low grade inflammation due to loss of immune tolerance plus insulin resistance. The authors conclude:
"CD44-VCAM-1 interaction mediates the adhesion between prostate cancer cells and HUVECs. IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through increasing VCAM-1 expression in the vascular endothelial cells. These findings suggest that IL-17 may act with insulin/IGF1 to promote prostate cancer metastasis."