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ORAL 07 - Lung Cancer Pathogenesis (ID 91)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
ORAL07.06 - Sox2 Cooperates with Lkb1 Loss to Promote Mouse Model of Squamous Cell Lung Cancer (ID 2910)
10:45 - 12:15 | Author(s): B. Witt
Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer with limited treatment options and a poor survival rate. Until recently, mouse models of SCC have been limited.
Using lentiviral delivery of Sox2 and Cre recombinase to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Mouse lungs were imaged for tumor formation using micro-CT imaging. Resulting mouse tumors were evaluated for histological markers including Nkx2.1, Sox2, p63, cytokeratin-5, cytokeratin-14 and compared to human squamous tumors. Phospho-signaling proteins including pAkt, pErk, pStat3, pAMPK, p4EBP1 were also evaluated in mouse and human tumors by immunohistochemistry.
Expression of Sox2 specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Importantly, Sox2 expression and mTOR pathway activation frequently co-occur in human squamous tumors. Mouse squamous tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. Sox2 expression is sufficient to induce phosphorylated Stat3 in vitro (Mukhopadhyay et al, Cell Reports, 2014). Sox2-driven tumors also exhibit immune cell infiltration consistent with other squamous lung cancer models.
This mouse model of Sox2-driven squamous lung cancer may be a useful model to study immunotherapies and their mechanism of action. This model may also be used to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery. Our data suggest mTOR, Jak-Stat and immunotherapies may be relevant targets for squamous lung cancer.
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