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Influence of Interactions between Lung Cancer Cells、Inflammatory Cell or Fetal Lung Fibroblast on Matrix Metalloproteinase-1, -2, -9 Expression and Inhibiting Effects of Retinoic Acid on Lung Tissue Destruction

Author: ZuoShengJie
Tutor: ZhuYunKui
School: Lanzhou University
Course: Department of Respiratory Medicine
Keywords: Matrix metalloproteinases H460 Mononuclear cells Lung Cancer Shift Three dimensional culture Embryo lung fibroblasts ATRA , neutrophil elastase Collagen
CLC: R734.2
Type: Master's thesis
Year: 2010
Downloads: 49
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Abstract

Stromal microenvironment of fibroblasts, inflammatory cells and other interactions affect tumor development and metastasis. MMP can degrade extracellular matrix and basement membrane components most affect tumor occurrence, development and metastasis. Experiment 1 Experiment 2 by the tumor stromal cells (fibroblasts, monocytes) on lung cancer MMP expression of 1,2,9, to investigate the stromal microenvironment of lung metastasis. Emphysema progressive damage to the alveolar wall, alveolar expansion of its characteristic lesions, in recent years there is evidence that the process of development of emphysema associated with complex extracellular matrix (ECM) remodeling process. Matrix metalloproteinases and their tissue inhibitors (MMPS / TIMPs) secretion and activation of runaway imbalance, in this process plays an important role. Recent studies have found that retinoic acid can reduce the expression of collagenase, and promote the repair of epithelial injury, increased elastin synthesis. Given the occurrence of emphysema clinically relevant elastase, the present study aimed to investigate the embryo lung fibroblasts in three-dimensional collagen activity to explore their culture in the lung tissue damage in the intervention, so as RA for human COPD provide the basis for prevention and treatment. This study is divided into three experiments: Experiment 1. Lung cancer H460 cells and mononuclear cell interactions on MMP-1, -2, -9 expression Objective: To study mononuclear cells and lung cancer H460 cells cultured on three-dimensional mixed-MMP- 1, MMP-2 and MMP-9 expression, and to observe the role of MMPs on collagen degradation. Methods: The activity of collagen-dimensional culture divided into control group (CG), H460 cell group (HG), mononuclear cell group (MG), mixed group (HMG) 4 groups to observe the growth of cancer cells condition. Gelatin zymography each group at different time points measured MMP-2 and MMP-9 expression, determined by Western blotting MMP-1. RESULTS: The cells were grown in three-dimensional collagen good; MG did not significantly secreted MMP-1, MMP-2 and MMP-9, HG and HMG are secreted MMP-1, MMP-2 and MMP-9, but HMG secretion was significantly More than HG. Experiment 2. Lung cancer H460 cells and mononuclear cells, embryonic lung fibroblast interactions on MMP-1, -2, -9 expression Objective: To study mononuclear cells, embryonic lung fibroblast and lung cancer H460 cells dimensional mixed Training for MMP-1, MMP-2 and MMP-9 expression, and to observe the role of MMPs on collagen degradation. Methods: The activity of collagen-dimensional culture divided into control group (CG), H460 cell group (HG), mononuclear cell group (MG), fetal lung fibroblast cell group (FG), H460 and mononuclear cells mixed group (HMG) , H460 and embryo lung fibroblasts mixed group (HFG), three cell co-culture group (HMFG) 7 group, observing the growth of cancer status was measured by gelatin zymography groups of MMP-2 and MMP-9 expression , determined by Western blotting MMP-1. RESULTS: The cells were grown in three-dimensional collagen good; CG and MG did not significantly secreted MMP-1, MMP-2 and MMP-9, other groups were secreted MMP-1, MMP-2 and MMP-9, but HMFG secretion MMP significantly more than other groups HG. Experiment 3. ATRA and elastase on lung tissue damage in rats Objective: embryonic lung fibroblast three-dimensional culture techniques, direct observation of all-trans retinoic acid and elastase a major component of the lung tissue collagen degradation of the intervention effect. Methods: In embryo lung fibroblasts dimensional culture process with cytokines (TNF-α and IL-1β) to induce the expression of MMPs, while adding RA or NE intervention MMPs or TIMPs expression; measured by gelatin zymography MMP -2, -9, determined by Western blotting MMP-1, -3, and TIMP-1, -2 (metalloproteinase inhibitor), and cultured for 5 days in the determination of collagen content and size of size. Results: TNF-α and IL-1β-induced three-dimensional collagen in cultured lung fibroblasts to produce MMP-1, 3 and 9, but caused only a small amount of collagen degradation (P gt; 0.05), while adding neutrophil elastase (NE), resulting in almost complete degradation of collagen (P lt; 0.01). NE to MMP-1, 2,3 and 9 the non-activated form into smaller molecular weight activated molecules, while TIMP-1 and -2 clear. RA inhibited the expression of MMP-1 and MMP-3, -9 activation and undermine NE on TIMP-1, -2 scavenging effect, thereby inhibiting the degradation of collagen. Matrix collagen degradation occurs after a strong contraction. There are more than three experiments the following conclusions: 1. Mixed inflammatory cells and cancer cells after culture, cell-cell interaction to promote increased secretion of MMPs; matrix metalloproteinases can degrade the extracellular matrix, thus contributing to lung cancer invasion and metastasis. 2 mononuclear cells, fibroblasts and cancer cells mixed culture, the cells secrete MMPs promote interaction; matrix metalloproteinases can degrade the extracellular matrix and other interstitial tissue, thus contributing to lung cancer invasion and metastasis. 3 matrix metalloproteinase directly degrade collagen and other interstitial lung tissue, causing destruction of lung tissue; neutrophil elastase induced through activation of matrix metalloproteinases or accelerate the destruction of the extracellular matrix; matrix metalloproteinases and elastase synergy effect may be emphysema and other lung tissue destruction mechanism. All-trans retinoic acid (RA) by inhibiting the expression and activation of MMPs elastase on lung tissue against the destructive effects.

Influence of Interactions between Lung Cancer Cells、Inflammatory Cell or Fetal Lung Fibroblast on Matrix Metalloproteinase-1, -2, -9 Expression and Inhibiting Effects of Retinoic Acid on Lung Tissue Destruction

Abstract

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