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

Author:

Lv Liang1,Zhang Shizhen2,Hu Yu1,Zhou Peizhi1,Gao Ling3,Wang Mengmeng1,Sun Zhen4,Chen Cheng1,Yin Senlin1,Wang Xiujie4,Jiang Shu1

Affiliation:

1. Department of Neurosurgery, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China

2. Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

3. Department of Abdominal Cancer, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China

4. Laboratory of Experimental Oncology, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China

Abstract

AbstractTumor-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.

Publisher

Georg Thieme Verlag KG

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine

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