Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-β1

Abstract

BackgroundAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with fibrous stromal invasion are newly introduced subtypes of small lung adenocarcinoma. AIS is a small localized adenocarcinoma in which growth is restricted to neoplastic cells along preexisting alveolar structures without fibrous stromal invasion. In MIA, by contrast, tumor cells have infiltrated the myofibroblastic stroma. Transforming growth factor (TGF)-β is known to be produced by progressor tumors, and excessive TGF-β contributes to a pathological excess of tissue fibrosis. TGF-β1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-β1 expression and clinicopathological microinvasion in patients with small lung adenocarcinoma.MethodsThe study participants were 45 patients who underwent curative surgery for AIS and MIA 3 cm or less in size. Those tumors were assessed based on immunohistochemical staining using anti-TGF-β1 antibody. The TGF-β1 status was assessed immunohistochemically using the Allred 8-unit system.ResultsThe rates of TGF-β1 positivity in the AIS and MIA groups were 27.3% and 65.2%, respectively (P <0.05). The median of Allred score was 0.5 (range 0–5) in the AIS group and 3.0 (range 0–6) in the MIA group (P = 0.0017).ConclusionsWe suggest that TGF-β1 expression is likely to be significantly stronger in patients with MIA than in those with AIS, and the increased expression may be associated with minimal invasion and infiltration of the myofibroblastic stroma.

MiR‐9 is involved in TGF‐β1‐induced lung cancer cell invasion and adhesion by targeting SOX7

“…Further, this study for the first time showed that miR‐9 knockdown suppressed NSCLC cell invasion and adhesion in vitro . TGF‐β1 is an important regulator in NSCLC metastasis . In the present study, we found TGF‐β1‐induced cell invasion and adhesion were also inhibited by miR‐9 knockdown.…”

“…In addition, SOX7 protein expression was regulated by miR‐9. TGF‐β1 has been implicated in the pathogenesis of lung cancers . Interestingly, in the present study, we found the expression of miR‐9 and SOX7 was up‐regulated by TGF‐β1 treatment in NSCLC cells, despite the observation that SOX7 was a direct target of miR‐9.…”

Role of TGF-β1 in Human Colorectal Cancer and Effects after Cantharidinate Intervention

“…Therefore, the prevention and treatment of mutant gene has an important significance. Recent studies showed, TGF-β could increase the invasiveness of cancer cells by increasing their proteolytic activity and promoting their binding to cell-adhesion molecules (Imai et al, 2013). In an earlier study, tumor-derived TGF-β1 induced dendritic cell apoptosis within lymph nodes in non-small cell lung cancer (Imai et al, 2013).…”

“…Recent studies showed, TGF-β could increase the invasiveness of cancer cells by increasing their proteolytic activity and promoting their binding to cell-adhesion molecules (Imai et al, 2013). In an earlier study, tumor-derived TGF-β1 induced dendritic cell apoptosis within lymph nodes in non-small cell lung cancer (Imai et al, 2013). Consistent with those findings, the effects of TGF-β1 on angiogenesis, stroma formation and immune function appear to further support tumor progression and invasion (Balasubramanian et al, 2002;Botaitis et al, 2013).…”

Transforming growth factor beta1 (TGFbeta1) in physiology and pathology

“…TGFb-induced expression of IGFBP-3 regulates IGF-I receptors signalling in human osteosarcoma cells [134]. Bronchioloalveolar invasion in NSCLC is associated with tumours expression of TGFb1 assessed with immunohistochemical staining using anti-TGFb1 antibody [135]. It was also found a higher concentration of TGFb1 (4.2 x) and TGFb2 (1.5 x) (but not TGFb3) in the blood of patients with metastatic malignant melanoma in contrast to the initial development chase which indicates a systemic immunosuppressive TGFb1 activity in the terminal stage of the disease [136].…”