title: Role of the extracellular matrix in variations of invasive pathways in lung cancers.
abstract: Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.
authors: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo São Paulo, SP, Brasil. vankaren@usp.br
authors: V K
authors: VK
authors: de Sá
authors: L
authors: L
authors: Carvalho
authors: A
authors: A
authors: Gomes
authors: A
authors: A
authors: Alarcão
authors: M R
authors: MR
authors: Silva
authors: P
authors: P
authors: Couceiro
authors: V
authors: V
authors: Sousa
authors: F A
authors: FA
authors: Soares
authors: V L
authors: VL
authors: Capelozzi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D014453:Glucuronosyltransferase / Q000032:analysis; D006801:Humans; D000076002:Hyaluronan Synthases; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009367:Neoplasm Staging
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases