Abstract
BackgroundGrowth hormone (GH) mainly serves an endocrine function to regulate somatic growth, but also serves an autocrine function in lung growth and pulmonary function. Several recent studies have demonstrated the role of autocrine GH in tumor progression in some organs. However, it is not clear whether excessive secretion of GH in the lungs is related to pulmonary nodule formation.MethodsFirstly, the lung tissues dissected from mice were used for Western blotting and PCR measurement. Secondly, the cultured cells were used for examining effects of GH on B16F10 murine melanoma cells. Thirdly, male C57BL/6 mice were intravenously injected with B16F10 cells and then subcutaneously injected with recombinant GH twice per week for three weeks. Finally, stably transfected pool of B16F10 cells with knockdown of growth hormone receptor (GHR) was used to be injected into mice.ResultsWe found that expression of GH was elevated in the lungs of DJ-1 knockout (KO) mice. We also examined the effects of GH on the growth of cultured melanoma cells. The results showed that GH increased proliferation, colony formation, and invasive capacity of B16F10 cells. In addition, GH also increased the expression of matrix metalloproteinases (MMPs) in B16F10 cells. Administration of GH in vivo enhanced lung nodule formation in C57/B6 mice. Increased lung nodule formation in DJ-1 KO mice following intravenous injection of melanoma cells was inhibited by GHR knockdown in B16F10 cells.ConclusionsThese results indicate that up-regulation of GH in the lungs of DJ-1 KO mice may enhance the malignancy of B16F10 cells and nodule formation in pulmonary metastasis of melanoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2898-5) contains supplementary material, which is available to authorized users.
Highlights
Growth hormone (GH) mainly serves an endocrine function to regulate somatic growth, and serves an autocrine function in lung growth and pulmonary function
DJ-1 is known as an oncogene, which reacts with activated Ras [4], a potential serum biomarker secreted from breast cancer cells [1] and malignant melanoma [5]
We aimed to examine whether there is a connection between lung GH expression and lung metastasis of growth hormone receptor (GHR)-expressing melanoma cells
Summary
Growth hormone (GH) mainly serves an endocrine function to regulate somatic growth, and serves an autocrine function in lung growth and pulmonary function. Several recent studies have demonstrated the role of autocrine GH in tumor progression in some organs It is not clear whether excessive secretion of GH in the lungs is related to pulmonary nodule formation. GH is mainly secreted from the anterior pituitary and plays an important role in an individual’s development [13] It binds to the growth hormone receptor (GHR) and exerts its effects through insulin-like growth factor-I (IGF-I) signaling, which controls cell proliferation, survival, and differentiation and enhances cell cycle progression in many cell types [14]. GHRs are expressed in lung epithelia to enable GH effects [16] and IGF-1 is widely expressed during rodent lung organogenesis [17] These findings indicate that autocrine functions of lung GH may enhance lung growth and survival of surrounding cells. The autocrine effects of GH on tumor cells in the lungs remain unclear
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