Author of

• 18971

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  P1.02 - Biology/Pathology (ID 614)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22507

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    P1.02-023 - TGF-β Signaling Mediated by Fibroblasts is Associated with the Histological Subtypes of Lung Adenocarcinoma (ID 8068)

    09:30 - 09:30  |  Presenting Author(s): Ryo Sato
    • Abstract

    Background:
    About 90% of invasive lung adenocarcinoma cases contain several histologic subtypes and demonstrate heterogenous histologic patterns. How such histological heterogeneity is formed remains unclear. The histological subtypes are associated with the prognosis in lung adenocarcinoma patients. Understanding the molecular mechanisms contributing to the pathological subtypes may provide a basis for developing new therapeutic strategies. Tumor microenvironments (TME) including endothelial cells, immune cells, and fibroblasts, have all been recognized as key components regulating cancer progression. TME influences tumor cells via direct cell-cell contact or their products, such as cytokines and extracellular matrixes. In this study, we determined the role of TME in the histological heterogeneity of lung adenocarcinoma.
    
    Method:
    We inoculated GFP-labeled A549 human lung adenocarcinoma cells into tissues in four different sites of immunodeficient mice including; the pleural cavity, subcutaneous region, intracardial, and the renal capsule. We then compared the histopathological features of those xenograft tumors. We established immortalized αSMA-positive cancer associated fibroblasts (CAFs) from the xenograft tumors, and co-cultured them with A549 cells in 3D culture conditions so as to analyze the interaction between the tumor cells and the stromal cells.
    
    Result:
    We found that the xenografted A549 cells developed distinct histological types of tumors; solid types and acinar types, depending on the inoculated sites. The solid type tumors contained an abundance of acidic mucins stained with Alcian blue, and they expressed MUC5AC, which is one of the common mucin core proteins. The acinar type tumors showed gland-like structures encircled by stromal cells. We found that the phosphorylation of Smad3 were upregulated in the acinar type tumors, especially αSMA-positive CAFs. Smad3 is the downstream of the transforming growth factor-β (TGF-β) signal. These data indicate that the TGF-β/Smad pathway is activated in acinar type tumors. CAFs derived from acinar type tumors induced acinar formations of A549 cells under in vitro 3D culture conditions. We also found that the inhibitor of TGF-β receptor I suppressed such acinar formations, suggesting that TGF-β signaling is associated with the histological subtypes of lung adenocarcinoma.
    
    Conclusion:
    Our data show that the histological heterogeneity of lung adenocarcinoma is dependent on TGF-β signaling mediated by the αSMA-positive CAFs. Inhibition of TGF-β signaling might block interactions between cancer cells and αSMA-positive CAFs, and TGF-β signaling inhibitors might suppress tumor heterogeneity in lung adenocarcinoma.
    
    

• 20194

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  P3.15 - SCLC/Neuroendocrine Tumors (ID 731)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: SCLC/Neuroendocrine Tumors
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 24216

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    P3.15-009 - Impact of Interstitial Lung Disease on Clinical Outcomes in Small Cell Lung Cancer Patients (ID 8583)

    09:30 - 09:30  |  Author(s): Ryo Sato
    • Abstract

    Background:
    The impact of interstitial lung disease (ILD) on the clinical outcome in small cell lung cancer (SCLC) patients has not been fully understood. The purpose of this study is to investigate the impact of ILD on treatment and survival in SCLC.
    
    Method:
    From April 2006 to March 2016, 67 SCLC patients treated with chemotherapy at Kumamoto University hospital were evaluated. Therapeutic response, progression-free survival (PFS) and overall survival (OS) were compared between SCLC with ILD (n=16) and SCLC without ILD (n=51).
    
    Result:
    Patients’ characteristics including age, sex, smoking, serum LDH, stage (limited/ extensive disease) between two groups were similar, except for lower proportion of chemoradiotherapy in SCLC with ILD (7% vs. 57%, P= <0.001). SCLC with ILD had a significantly lower objective response rate than SCLC patients without ILD (50% vs. 84%, P= 0.005). SCLC patients with ILD had a significantly shorter PFS (median, 184 days vs. 290 days, P= 0.008) and OS (median, 241 days vs. 704 days, P= <0.001) than patients without ILD. In addition, multivariate analysis for PFS and OS revealed that the coexisting ILD was independent predictive factor for poor survival in SCLC patients treated with chemotherapy (PFS, hazard ratio [HR] 2.06, 95% confidence interval [CI], 1.01-4.18, P= 0.046, OS, HR 3.29, 95% CI 1.53-7.08, P= <0.002). Acute exacerbation of ILD was observed in 31% of SCLC patients with ILD.
    
    Conclusion:
    This study suggests that coexisting ILD is a predictive factor for poor PFS and OS in SCLC treated with chemotherapy.