TY - JOUR
T1 - Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas
AU - Cai, Lin
AU - Leng, Zhi Gen
AU - Guo, Yu Hang
AU - Lin, Shao Jian
AU - Wu, Ze Rui
AU - Su, Zhi Peng
AU - Lu, Jiang Long
AU - Wei, Li Fei
AU - Zhuge, Qi Chuan
AU - Jin, Kunlin
AU - Wu, Zhe Bao
N1 - Funding Information:
We are grateful to Prof. Xun Zhang (Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114) for his critical evaluation and linguistic revision of this manuscript. This project was funded by grants from the National Natural Science Foundation of China (81271523 and 81471392 to Z.B.W) and from the Zhejiang Open Foundation of the Top Key Discipline (LKYJ015 to Z.B.W).
Funding Information:
We are grateful to Prof. Xun Zhang (Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114) for his critical evaluation and linguistic revision of this manuscript. This project was funded by grants from the National Natural Science Foundation of China (81271523 and 81471392 to Z.B.W) and from the Zhejiang Open Foundation of the Top Key Discipline (LKYJ015 to Z.B.W).
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.
AB - Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.
KW - Angiogenesis
KW - Bromocriptine
KW - Dopamine agonist
KW - Endocan
KW - Endothelial cell-specific molecule 1
KW - Prolactinoma
UR - http://www.scopus.com/inward/record.url?scp=84949636903&partnerID=8YFLogxK
U2 - 10.1007/s12020-015-0824-2
DO - 10.1007/s12020-015-0824-2
M3 - Article
C2 - 26662185
AN - SCOPUS:84949636903
SN - 1355-008X
VL - 52
SP - 641
EP - 651
JO - Endocrine
JF - Endocrine
IS - 3
ER -