Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway

Capsule:
The ESC-derived CCL2 enhances the expression of proliferating cell nuclear antigen, survivin, and matrix metalloproteinase-2, decreases tissue inhibitor of metalloproteinase 1/2 expression, and promotes the growth and invasiveness of ESCs in an autocrine manner through the Akt and MAPK/Erk1/2 signal pathway.

Authors:
Ming-Qing Li, M.D., Ph.D., Hua-Ping Li, M.D., Ph.D., Yu-Han Meng, M.S., Xiao-Qiu Wang, M.D., Ph.D., Xiao-Yong Zhu, M.D., Ph.D., Jie Mei, B.Sc., Da-Jin Li, M.D., Ph.D.
Volume 97, Issue 4 , Pages 919-929.e1, April 2012

Objective:
To clarify the role and mechanism of CCL2 in regulating the biological functions of endometrial stromal cells (ESCs).

Design:
The CCL2 effect on the viability, proliferation, and invasion in the eutopic ESCs from endometriosis.

Setting:
Research laboratories.

Patient(s):
Patients with endometriosis aged 23–47 years.

Intervention(s):
None.

Main Outcome Measure(s):
Signal transduction and downstream molecules from CCR2.

Result(s):
We have found that the secretion of CCL2 by the eutopic ESCs from endometriosis is higher than that of healthy ESCs without endometriosis. The CCL2 can enhance the viability, proliferation, and invasion of ESCs in a dosage and time-dependent manner. Anti-CCL2 neutralizing antibody and CCR2 antagonist can completely abolish the increase in viability, proliferation, and invasiveness of ESCs induced by CCL2. The CCL2 can increase the expression of proliferating cell nuclear antigen, survivin, and matrix metalloproteinase 2, and decrease the expression of tissue inhibitor of metalloproteinase 1 and 2, and promote the viability, proliferation and invasiveness of ESCs by activating Akt and MAPK/Erk1/2 signal pathway, but not p38 and JNK signal pathway.

Conclusion(s):
CCL2 might play an important role in regulating the functions of ESCs through Akt and MAPK/Erk1/2 signal pathway, and overexpression of CCL2 in ESCs and peritoneal fluid (PF) would lead to onset and development of endometriosis.

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