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S.M. Janes
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MA12 - Miscellaneous Biology/Pathology (ID 476)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
- Moderators:B. Dome, W.D. Travis
- Coordinates: 12/06/2016, 14:20 - 15:50, Schubert 1
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MA12.02 - MMP12 and LMO7, Two Key Players on opposite Sides of Early Lung Squamous Cell Carcinoma Development (ID 5882)
14:20 - 15:50 | Author(s): S.M. Janes
- Abstract
- Presentation
Background:
Our laboratory has a unique cohort of patients with pre-invasive lung squamous cell carcinoma (SqCC) lesions, within which there is a clear discrepancy between the prevalence of pre-invasive lesions and the incidence of lung cancer, suggesting that not all pre-invasive lesions progress to cancer. Using gene expression microarrays we identified 1846 genes significantly differentially expressed between progressive and regressive pre-invasive SqCC lesions. The macrophage metalloelastase MMP12 gene was found to be highly expressed in progressive lesions, and we hypothesised that it plays a role in epithelial-to-mesenchymal transition (EMT). Conversely, the actin binding protein LIM-domain only 7 (LMO7) gene was highly expressed in regressive lesions, and we postulated that it may be protective against EMT due to its role in the maintenance of epithelial architecture. Initial studies using three SqCC cell lines (A431, H357 and H376) with MMP12-shRNA knockdown showed a significant decrease in migration and invasion compared to non-silencing shRNA controls. LMO7-shRNA knockdown in HBECs was found to significantly increase migration. The aim of this study is to further characterise the function and signalling of MMP12 and LMO7 in lung SqCC development.
Methods:
Eight-week-old NOD/SCID mice were used for tumorigenesis experiments. A431 and H357 MMP12-shRNA knockdown and non-silencing shRNA cells were injected in a suspension of one million cells in a total of 200μl, subcutaneously in the right and left flank, respectively. Tumours were measured every 2–5 days. Adhesion assays were carried out to assess the roles of MMP12 knockdown or LMO7 overexpression on cell adhesion. Cell signalling mechanisms were assessed using western blotting, qPCR and immunostaining.
Results:
We observed that MMP12 knockdown decreases tumorigenicity in an immunocompromised mouse model. Both A431 and H357 MMP12 knockdown cells produced significantly smaller tumours compared with non-silencing shRNA cells. We found that MMP12 knockdown decreases cell adhesion, which is currently being further investigated along with effects on integrin signalling pathways. Levels of EMT markers were assessed in MMP12 knockdown and LMO7 overexpressing cells using qPCR, western blotting and immunostaining. Results indicate that higher MMP12 expression is associated with a mesenchymal phenotype, whereas higher LMO7 expression is associated with an epithelial phenotype.
Conclusion:
Our results suggest that MMP12 is a key driver of migration and invasion in SqCC and its high expression may contribute to EMT, whereas LMO7 is a putative tumour suppressor with a crucial role in maintaining epithelial cell architecture. MMP12 and LMO7 may be potential therapeutic markers for lung cancer at an early stage.
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MTE14 - How to Implement Screening/Early Detection in Routine Practice (Ticketed Session) (ID 308)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Schubert 6
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MTE14.01 - How to Implement Screening/Early Detection in Routine Practice (ID 6565)
07:30 - 08:30 | Author(s): S.M. Janes
- Abstract
- Presentation
Abstract not provided
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-010 - Characteristics of Lung Cancer Patients Diagnosed Following Emergency Admission (ID 5091)
14:30 - 15:45 | Author(s): S.M. Janes
- Abstract
Background:
The proportion of patients with cancers diagnosed via the emergency route and their demographic characteristics vary according to tumour type[1]. Patients with lung cancers diagnosed as emergency presentations suffer worse outcomes[2]. The aim of this observational study was to determine the characteristics of a sample of patients with new lung cancers presenting through the emergency route.
Methods:
Clinical and demographic patient data were extracted from the London Cancer Registry. Data relating to emergency presentations of lung cancer were collected prospectively between January and August 2013 from nine acute trusts across northeast and central London and west Essex. Clinical and demographic characteristics were collated. The total number of emergency presentations were compared to the total numbers of lung cancers diagnosed within the same region over the corresponding time frame from the National Lung Cancer Audit data (NLCA).
Results:
Figure 1From the NLCA, there were an estimated 964 lung cancers recorded within the London cancer region during the study period. Of these, 310 (32%) lung cancers were recorded in the London Cancer registry as having presented via the emergency route. The median age of these patients was 73. The majority of patients were white and from areas of increased social deprivation. The proportion of patients presenting with stage IV disease was 67%, while 58% had a performance status of 0-2. The most common presenting symptoms were respiratory. 95% of patients were treated with palliative rather than curative intent.
Conclusion:
Approximately one third of new lung cancers within London Cancer are diagnosed following emergency admission. The next phase of work includes incorporating results from the London Cancer Alliance to provide pan-London data and to develop tools in primary care to identify these patients prior to emergency admission.
