Abstract 1880: Bulk lung cancer cell migration is more common than single cell migration and regulated by different genes

Autor: Sylvia Eidenhammer, Helmut Popper
Rok vydání: 2017
Předmět:
Zdroj: Cancer Research. 77:1880-1880
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2017-1880
Popis: Introduction: There are two different forms how tumor cells migrate: single cell or small cell cluster movement as it is seen in small cell carcinoma, and movement by large clusters of organized cells as seen most often in adenocarcinoma or squamous cell carcinoma. This latter migration form is not understood. Drosophila border cells forming wings migrate in large cell complexes similar to what is seen in the carcinomas and the genes identified in these cells might regulate the same process in carcinomas. Methods: 30 cases of pulmonary squamous cell and adenocarcinomas were selected based on the identification of large tumor cell clusters visible within the stroma as well as in blood vessels. Immunohistochemistry was done for receptor of activated C kinase (Rack1), brinker (brk), mother against dpp (mad), and saxophone (sax), proteins shown to be responsible for bulk cell movement in drosophila development. In addition immunohistochemistry was also done for Src-kinase, Twist, Snail, and TGFβ1 Tyrosine kinase substrate 5 (Tks5), E-cadherin, SARI (suppressor of AP-1), and vimentin, all known to be associated with epithelial-to-mesenchymal transition (EMT) and formation of invadopodia. Results and Conclusion: Most well differentiated pulmonary carcinomas migrate in large cell clusters, for example acinar adenocarcinomas form nicely structured acini deep within the stroma and even within blood vessels. These carcinomas do not undergo classical EMT. Proteins expressed by the four genes (Rack1, brk, mad, and sax) associated with border cell movement in drosophila could also be identified in pulmonary carcinomas and might coordinate bulk cell movement. Other members of TGF-beta signaling cascade were identified. Inhibition of Src by Rack1 may be important for border cell migration and cluster cohesion maintenance. Proteins usually seen in single tumor cell migration, such as vimentin (a sign of EMT) could not be proven in the tumor cell clusters. Findings of this study show that similar mechanisms are working in pulmonary carcinomas and that bulk cell migration is probably another way of metastasis. Further investigation using cell culture system and genetically designed adenocarcinomas expressing these genes should prove our findings and contribute in understanding migration of carcinoma bulk complexes. Citation Format: Helmut H. Popper, Sylvia Eidenhammer. Bulk lung cancer cell migration is more common than single cell migration and regulated by different genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1880. doi:10.1158/1538-7445.AM2017-1880
Databáze: OpenAIRE