| Lung cancer is a frequent malignancy with poor prognosis nowadays, of which 80% are non small cell lung cancer(NSCLC). Lymphatic metastasis is the primary way of lung cancer metastasis, and is an important reason of lung cancer causing death. Recent studies have confirmed that tumors may have the ability to increase lymphatic microvessel density within its surrounding, which facilitates the metastasis of tumor cells.VEGF family is the first to be discovered as lymphangiogenesis factor, and this finding has promoted further research about lymphangiogenesis.Later studies shows that PDGFs also enable the process of functional lymphatics formation,they can connect the receptors on the LEC. to promote LEC's proliferation.migration an the formation of tubular structures, which induce lymphangiogenesis. PDGFR-(3 is one of the receptors of PDGFs, mainly expressed in stroma cells. PDGFR-βplays an important role in the process of growth and development. Recent studies have confirmed that PDGFR-βis related with lymphatic metastasis in gastric cancer. Podoplanin is one of the specific molecular markers of LEC and related with lymphangiogenesis and lymphatic metastasis in CAFs.Stroma cells, together with extracellular matrix components, provide the microenvironment that is pivotal for cancer cell growth, invasion and metastatic progression. Characteristic stroma alterations accompany or even precede the malignant conversion of epithelial cells. Crucial in this process are cancer-associated fibroblasts (CAFs) that are located in the vicinity of the neoplastic epithelial cells. 'CAFs are marked byα-SMA.They are able to modify the phenotype of the epithelial cells by direct cell-to-cell contacts, through soluble factors or by modification of extracellular matrix components. Recent studies have confirmed novel data on the essential crosstalk between cancer cells and cells of the tumor stroma. with an emphasis on the role played by CAFs. In this paper we study the PDGFR-β, Podoplanin expression in NSCLC and the relationship between the lymphangiogenesis of NSCLC and PDGFR-β, Podoplanin expression, in order to provide a reference for further study of lymphangiogenesis and lymphatic metastasis.Objective:Detection the protein level expression of PDGFR-β, Podoplanin in the interstitial of NSCLC, and analysis the relationship between PDGFR-β, Podoplanin expression and CAFs and lymphangiogenesis.Methods:Applying the immunohistochemical Elivision method, CAFs were labeled byα-SMA, lymphatic vessels and expressions of PDGFR-βand Podoplanin were detected in 80 NSCLC and 20 adjacent normal tissues. And the lymphatic micro-vessel density (LMVD) by D2-40 as the specific marker of lymphatic endothelium was counted. The relationship of PDGFR-βand Podoplanin to CAFs, LMVD and the clinicopathological features of non-small cell lung cancer were then analyzed. We use SPSS 18.0 statistical software for statistical analysis, when P<0.05, there was a significant difference.Results:1. The expression of PDGFR-βin NSCLC The expressions of PDGFR-βin the interstitial of NSCLC were higher than that of adjacent normal tissues [46.35%(39/80) vs 20%(4/20), P<0.05]. Expression of PDGF-βwere closely related with CAFs. LMVD was significantly higher with PDGFR-β-positive expression than these with negative expression[(27.63±15.46) vs (17.47±14.68).t=3.01, P<0.05].The expression of PDGFR-βin the interstitial of NSCLC was correlated with differentiation(P<0.05).2. The expression of Podoplanin in NSCLC Specimens are Podoplanin positive in cytoplasmas in the interstitial of NSCLC. The expressions of Podoplanin were higher than that of adjacent normal tissues [55.00%(44/80) vs 10%(2/20), P<0.05]. Expression of Podoplanin were closely related with CAFs. LMVD was significantly higher with Podoplanin-positive expression than these with negative expression (27.70±17.68) vs (15.96±9.84),t=3.74, P<0.05]. The expression of Podoplanin in the interstitial of NSCLC was correlated with differentiation and lymph node metastasis (both P<0.05)3. The expression of PDGFR-βwas related with the expression of Podoplanin in stroma of NSCLC.4.CAFs in NSCLC CAFs was marked byα-SMA.α-SMA positive staining mainly located in the cytoplasm in all specimens, brownish yellow, this can confirm that CAFs are in all specimens.Conclusions:1. Overexpressions of PDGFR-βand Podoplanin can promote lymphangiogenesis and lymphatic metastasis, and study of those relevant inhibitors may make great good to patients with lymphatic and distal metastasis in NSCLC.2. Specimens are PDGF-βand Podoplanin positive in the region of a-SMA expression.Expression of PDGF-βand Podoplanin were closely related with CAFs,this can provide new ideas for tumor microenvironment and CAFs studies. |
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