Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma.
The death rates of hepatocellular carcinoma (HCC) are extremely high due to the paucity of therapeutic options. Animal models and anecdotal clinical evidence indicate a potential role of hGH and hPRL in HCC. However, the prognostic relevance and the functional role of tumor expression of these hormones in human HCC are not defined. Herein, we analyzed the mRNA and protein expression of hGH and hPRL in histopathological samples of non-neoplastic liver and HCC by in situ hybridization, PCR and immunohistochemistry techniques. Increased mRNA and protein expression of both hormones was observed in HCC compared with non-neoplastic liver tissues. hGH expression was significantly associated with tumor size and tumor grade. No significant association was observed between the expression of hPRL and any histopathological features. Amplification of both hGH and hPRL genes in HCC was observed when compared to non-neoplastic tissue. Expression of both hGH and hPRL was associated with worse relapse-free and overall survival in HCC patients. In vitro and in vivo functional assays performed with HCC cell lines demonstrated that autocrine expression of hGH or hPRL in HCC cells increased STAT3 activation, oncogenicity and tumor growth while functional antagonism with hGH-G120R significantly reduced these parameters. Hence, tumor expression of hGH/hPRL is associated with a worse survival outcome for patients with HCC and hGH/hPRL function as autocrine/paracrine promoters of HCC progression.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Xiangjun
X
Kong
Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Wenyong
W
Wu
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Yan
Y
Yuan
Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore.
Vijay
V
Pandey
Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
Zhengsheng
Z
Wu
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Xuefei
X
Lu
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Weijie
W
Zhang
Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore.
Yijun
Y
Chen
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Mingming
M
Wu
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Min
M
Zhang
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Gaopeng
G
Li
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Sheng
S
Tan
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Pengxu
P
Qian
Liggins Institute, University of Auckland, Auckland, New Zealand.
Jo K
JK
Perry
Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore.|National University Cancer Institute of Singapore, National University Health System, Singapore.
Peter E
PE
Lobie
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
Tao
T
Zhu
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D064593:Heterografts; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D019899:Paracrine Communication / Q000502:physiology; D011379:Prognosis; D011388:Prolactin / Q000378:metabolism*
D019382:Human Growth Hormone; D011388:Prolactin
growth hormone; hepatocellular carcinoma; oncogenicity; prolactin; survival