Markers of Stroma in Lung Cancer: Influence of COPD / Marcadores estromales en el cáncer de pulmón: la influencia de la enfermedad pulmonar obstructiva crónica

BACKGROUND: Stroma, mainly composed by fibroblasts, extracellular matrix (ECM) and vessels, may play a role in tumorigenesis and cancer progression. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for LC. We hypothesized that markers of fibroblasts, ECM and endothelial cells may differ in tumors of LC patients with/without COPD. METHODS: Markers of cultured cancer-associated fibroblasts and normal fibroblasts [CAFs and NFs, respectively, vimentin and alpha-smooth muscle actin (SMA) markers, immunofluorescence in cultured lung fibroblasts], ECM, and endothelial cells (type I collagen and CD31 markers, respectively, immunohistochemistry) were identified in lung tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 15 LC-COPD patients and 15 LC-only patients. RESULTS: Numbers of CAFs significantly increased, while those of NFs significantly decreased in tumor samples compared to non-tumor specimens of both LC and LC-COPD patients. Endothelial cells (CD31) significantly decreased in tumor samples compared to non-tumor specimens only in LC patients. No significant differences were seen in levels of type I collagen in any samples or study groups. CONCLUSIONS: Vascular endothelial marker CD31 expression was reduced in tumors of non-COPD patients, while type I collagen levels did not differ between groups. A rise in CAFs levels was detected in lung tumors of patients irrespective of airway obstruction. Low levels of CD31 may have implications in the overall survival of LC patients, especially in those without underlying airway obstruction. Identification of CD31 role as a prognostic and therapeutic biomarker in lung tumors of patients with underlying respiratory diseases warrants attention

ANTECEDENTES: El estroma, compuesto principalmente por fibroblastos, matriz extracelular (MEC) y vasos, puede desempeñar un papel en la génesis tumoral y la progresión del cáncer. La enfermedad pulmonar obstructiva crónica (EPOC) es un factor de riesgo independiente para el carcinoma de pulmón (CP). Nuestra hipótesis fue que los marcadores de fibroblastos, MEC y células endoteliales pueden variar en los tumores de los pacientes con CP con o sin EPOC. MÉTODOS: Se identificaron los marcadores de fibroblastos asociados al cáncer y los fibroblastos normales cultivados (FAC y FN, respectivamente; marcadores: vimentina y α-actina del músculo liso [SMA por sus siglas en inglés]; inmunofluorescencia en fibroblastos de pulmón cultivados) y marcadores de la MEC y las células endoteliales (marcadores: colágeno tipo I y CD31, respectivamente; inmunohistoquímica) en muestras de pulmón tumoral y no tumoral (toracotomía para resección de tumores pulmonares) de 15 pacientes con EPOC-CP y 15 pacientes con solo CP. RESULTADOS: El número de FAC aumentó de forma significativa, mientras que el de FN disminuyó significativamente en las muestras tumorales en comparación con las muestras no tumorales de pacientes con CP y EPOC-CP. Las células endoteliales (CD31) disminuyeron también de forma significativa en las muestras tumorales en comparación con las muestras no tumorales solo en los pacientes con CP. No se observaron diferencias significativas en los niveles de colágeno tipo I en ninguna muestra o grupo de estudio. CONCLUSIONES: La expresión del marcador vascular endotelial CD31 se redujo en los tumores de los pacientes sin EPOC, mientras que los niveles de colágeno tipo I no difirieron entre los grupos. Se detectó un aumento en los niveles de FAC en los tumores de pulmón de los pacientes, con independencia de la presencia de obstrucción de las vías respiratorias. Los niveles bajos de CD31 pueden tener implicaciones en la supervivencia general de los pacientes con CP, en especial, en aquellos sin obstrucción subyacente de las vías respiratorias. Convendría estudiar e identificar el papel del CD31 como biomarcador terapéutico y de pronóstico en los tumores de pulmón de pacientes con enfermedades respiratorias subyacentes

Markers of Stroma in Lung Cancer: Influence of COPD.

BACKGROUND: Stroma, mainly composed by fibroblasts, extracellular matrix (ECM) and vessels, may play a role in tumorigenesis and cancer progression. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for LC. We hypothesized that markers of fibroblasts, ECM and endothelial cells may differ in tumors of LC patients with/without COPD. METHODS: Markers of cultured cancer-associated fibroblasts and normal fibroblasts [CAFs and NFs, respectively, vimentin and alpha-smooth muscle actin (SMA) markers, immunofluorescence in cultured lung fibroblasts], ECM, and endothelial cells (type I collagen and CD31 markers, respectively, immunohistochemistry) were identified in lung tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 15 LC-COPD patients and 15 LC-only patients. RESULTS: Numbers of CAFs significantly increased, while those of NFs significantly decreased in tumor samples compared to non-tumor specimens of both LC and LC-COPD patients. Endothelial cells (CD31) significantly decreased in tumor samples compared to non-tumor specimens only in LC patients. No significant differences were seen in levels of type I collagen in any samples or study groups. CONCLUSIONS: Vascular endothelial marker CD31 expression was reduced in tumors of non-COPD patients, while type I collagen levels did not differ between groups. A rise in CAFs levels was detected in lung tumors of patients irrespective of airway obstruction. Low levels of CD31 may have implications in the overall survival of LC patients, especially in those without underlying airway obstruction. Identification of CD31 role as a prognostic and therapeutic biomarker in lung tumors of patients with underlying respiratory diseases warrants attention.