PURPOSE: Clinical studies reported a good prognosis for patients with small-sized Bronchiolo-alveolar carcinoma (BAC) of the lung in which cancer cells spread on the internal surface of alveoli, but did not infiltrate interstitially. In contrast, the prognosis of patients with BAC containing actively proliferating fibroblasts is poor, with cancer cells invading frequently into micro-vessels. The importance of cancer-stroma communication for the development of the invasive component of BAC was reported previously. In this report, cancer-stroma interaction for the development of the invasive component of BAC was investigated with both in-vitro experimental model and clinical specimens.
METHODS: A. Mixture of A549 (bronchiolo-alveolar carcinoma of lung) and WI38 (fibroblast) were encapsulated in DL-CGH, which we newly established for in vitro cell invasion assay. With this system, the cells in which the adhesion moleculaes were transiently suppressed by RNAi were studied. B. 127 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Adhesion molecules. The relationship between expression of molecules and clinicopathological features was analyzed, and the influence of molecules expression on outcome in these patients was assessed.
RESULTS: A. The significant increase in cell invasiveness was observed in DL-CGH containing cells transfected with E-cadherin siRNA. B. The disease-free survival rate of patients with positive Necl-5 overexpression was significantly lower than in those with negative Necl-5 overexpression (p=0.0004).
CONCLUSION: In-vitro data supported previously published clinical reports demonstrating a correlation between down-regulated E-cadherin expression and increased cancer cell invasiveness and metastasis. Clinical investigations indicated that Necl-5 played a role in mediating tumor cell invasion and that the overexpression of Necl-5 in cancer cells had clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma.
CLINICAL IMPLICATIONS: The overexpression of Necl-5 could be applicable as a reference index of molecular staging to select patients at high risk of recurrence who may benefit from intensive adjuvant therapy. Adhesion Molecules might be molecular targets to control BAC cell invasion.
DISCLOSURE: Yoshimasa Maniwa, No Financial Disclosure Information; No Product/Research Disclosure Information