Author of

• 11503

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  P2.03 - Poster Session 2 - Technology and Novel Development (ID 151)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11506

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    P2.03-003 - Two groups of lung adenocarcinoma cell lines that show distinct morphology and cancer-stromal interaction in 3 dimensional culture and mouse xenograft (ID 262)

    09:30 - 09:30  |  Author(s): D. Matsubara
    • Abstract

    Background
    We previously reported that lung adenocarcinoma cell lines could be classified into two groups according to gene expression patterns (Matsubara et al. Am J Pathol 2010). Group 1 cell lines expressed bronchial epithelial markers (CK7, MUC1, TTF-1) at high levels, while Group 2 cell lines showed epithelial-mesenchymal transition (EMT) phenotype (low-E-cadherin and high vimentin) and reduced expression of the bronchial epithelial markers. All cell lines mutated for EGFR, MET, HER2, and a cell line, LC-2/ad, recently found to harbor CCDC6-RET fusion (Matsubata, et al. J Thorac Oncol 2012), belonged to Group 1, and expressed EGFR, MET, HER3 at high levels, while KRAS-mutated cells lines were equally distributed in the two groups. Also, these two groups showed distinct sensitivity for gefitinib and cisplatin, respectively (Matsubara et al. J Thorac Oncol 2010, 2012). Here we tested the relevance of this classification for morphology and cancer-stromal interaction in 3 dimensional culture and mouse xenograft.

    Methods
    The 40 lung carcinoma cell lines consisted of 35 adenocarcinomas, 4 large cell carcinomas, and 1 adenosquamous carcinoma. These cells were plated onto Matrigel with or without lung-derived fibroblasts. Cell lines were also allowed to form spheroid in suspension culture, and then plated into collagen gel with or without lung-derived fibroblasts. To form xenograft tumors, cell lines were injected subcutaneously into NOD/SCID mice and allowed to form tumors, and resulting tumors were subjected to histologic analysis at 4-8 weeks.

    Results
    We demonstrated that on Matrigel essentially all Group 1 cell lines formed round spheroid, while Group 2 cell lines formed either round, stellate, or grape-like spheroid. Round spheroid forming cells remained non-invasive in monoculture, but upon co-culture with fibroblast, they acquired the ability to invade into Matrigel or collagen gels. In contrast, Groups 2 cell lines that formed stellate or grape-like spheroid showed invasive growth in monoculture, and co-culture with fibroblast seemed to enhance the invasive growth in some, but not all Groups 2 cell lines. Thus, Group 1 cell line required stromal fibroblast for invasion, while most Group 2 cell lines are endowed the ability to invade the stroma on their own. Consistent with this notion, when subcutaneously injected into immunocompromized mice, essentially all tumors derived from Group 1 cell lines were enriched with stromal fibroblast, while most tumors derived from Group 2 cell lines exhibited medullary histology with scanty stromal fibroblast.

    Conclusion
    Collectively, the data suggest that our two-way classification based on gene expression pattern has relevance for genetic, morphologic, and biologic properties of lung adenocarcinomas.