Mast cell chymase affects the proliferation and metastasis of lung carcinoma cells in vitro

Abstract

Abstract. Metastasis of lung carcinoma cells is a major cause of organ failure and mortality of patients with lung cancer. Lung mast cells are a type of immune cell which reside in the respiratory mucosa. High numbers of mast cells are associated with the majority of common types of cancer; however, the effects of mast cells on cancer remain unclear. In the present study, the effects of mast cell chymase (MCC) on the proliferation and adhesion of the lung carcinoma cell lines A549 and H520 was investigated. After 24 h of treatment, the highest dose of MCC (50 mU/ml) decreased the proliferation rate of A549 and H520 cells, whereas the lowest dose of MCC (5 mU/ml) resulted in a small increase in the viability. A549 cells treated with MCC lost adhesion ability in a MCC dose-dependent manner; however, these detached cells were able to regrow when transferred to a fresh culture. The protein expression of epithelial (E-) cadherin, p53 and p21 in A549 lung carcinoma cells were detected by western blot analysis. The results of the present study revealed that, following 24 h of treatment, the expression level of E-cadherin was decreased, the p53 tumor suppressor protein was expressed in limited quantities and the expression of p21 was decreased. Zymography was used to examine the effects of MCC on the expression and activation of matrix metalloproteinase-9 (MMP-9) in A549 and H520 cells. The expression of MMP-9 in the two cell lines was time-and MCC dose-dependent. The results of the present study demonstrated that MCC stimulated lung carcinoma cell proliferation and adhesion, as well as regulated E-cadherin expression and the cell cycle, all of which are associated with cancer metastasis. Therefore, MCC may be a potential candidate for lung carcinoma therapy.

Role of Mast Cells in Shaping the Tumor Microenvironment

“…MC chymase Dose-dependent chymase decreased the rate of proliferation of both cell lines after 24 h post treating. It also hampered the A549 cells adhesion ability, downregulated the expression of E-cadherin [33] Glioma cell lines U2987MG and U3086MG…”

“…It is also reported that chymase increases the expression of MMP-9 in tumor cells. Chymase therefore promotes the separation, proliferation, and relocation of cell clusters through acting directly and indirectly on ECM to support metastasis [33].…”

Prostatik Adenokarsinomlarda Triptaz ve Kimaz Ekspresyon Farklılıkları

“…27 Studies conducted on mast cells containing chymase have led to the conclusion that chymase may be associated with tumor cell proliferation and metastasis. 43 In this study, mast cell distribution containing chymase was found to be mostly intratumoral (P=0.007). It is thought to be associated with tumor progression.…”

“…In conclusion, recent studies appear to suggest that MCT and MCTC may represent a promising target in cancer treatment due to its proangiogenic activity. [43][44][45] However, the character of MCT and MCTC expression in cancer types needs to be understood better. In our study, MCT expression in prostate carcinoma (intratumoral areas and peritumoral areas) were observed to be higher.…”

Renin-Angiotensin System in Lung Tumor and Microenvironment Interactions

“…Furthermore, tumor sections from 32 cases of adenocarcinoma and 13 cases of squamous cell carcinoma revealed significantly higher counts of chymase-positive mast cells in the central region than those in the normal regions [28]. Chymase has been associated with TGF-β activation and endothelin-1 formation from preproendothelin-1 in pulmonary fibrosis and chronic obstructive pulmonary disease [26], and in proliferation, adhesion, regulation of E-cadherin expression, and modulation of immunosuppressive microenvironment in lung carcinoma [29,30]. This effect is likely due to TGF-β inhibitory effect on T-cell proliferation and effector activity.…”