Exp Clin Endocrinol Diabetes 2018; 126(04): 213-221
DOI: 10.1055/s-0043-119636
Article
© Georg Thieme Verlag KG Stuttgart · New York

Invasive Pituitary Adenoma-Derived Tumor-Associated Fibroblasts Promote Tumor Progression both In Vitro and In Vivo

Liang Lv*
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Shizhen Zhang*
3   Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
,
Yu Hu*
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Peizhi Zhou
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Ling Gao
4   Department of Abdominal Cancer, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Mengmeng Wang
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Zhen Sun
2   Laboratory of Experimental Oncology, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Cheng Chen
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Senlin Yin
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Xiujie Wang
2   Laboratory of Experimental Oncology, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
,
Shu Jiang
1   Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China
› Author Affiliations
Further Information

Publication History

received 07 August 2017
first decision 07 August 2017

accepted 11 September 2017

Publication Date:
08 November 2017 (online)

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Abstract

Tumor-associated fibroblasts are the most abundant population in tumor stroma and impact on tumor initiation and progression. However, the biological function of tumor-associated fibroblasts in pituitary adenomas has not been fully elucidated to date. So, this study aims to clarify the function and significance of primary cultured pituitary adenoma-derived tumor-associated fibroblasts on rat pituitary adenoma cells. We identified primary cultured tumor-associated fibroblasts and normal fibroblasts based on the expression of α-smooth muscle actin as well as morphology. Furthermore, we investigated cell biological influences on rat pituitary adenoma cells through indirectly co-culturing tumor-associated fibroblasts with GH3 cells and subcutaneous xenograft model. All sorts of fibroblasts showed positive staining for α-smooth muscle actin. But α-smooth muscle actin and vascular endothelial growth factor highly expressed in invasive pituitary adenoma-derived tumor-associated fibroblasts compared to non-invasive pituitary adenoma-derived tumor-associated fibroblasts and normal fibroblasts. Besides, invasive pituitary adenoma-derived tumor-associated fibroblasts promoted the proliferation of GH3 cells in vitro as well as tumor growth in vivo. Finally, vascular endothelial growth factor was highly expressed in tumor specimens co-injected with invasive pituitary adenoma-derived tumor-associated fibroblasts. Our results suggested that invasive pituitary adenoma-derived tumor-associated fibroblasts displayed apparent growth promotion effects on rat pituitary cells both in vitro and in vivo accompanied by over-expression of vascular endothelial growth factor in invasive pituitary adenoma-derived tumor-associated fibroblasts and tumor specimens.

* Lv, Zhang and Hu contributed equally in this manuscript as the co-first authors