372 research outputs found
Abstract 1880: Bulk lung cancer cell migration is more common than single cell migration and regulated by different genes
No full textAbstract
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</jats:p
The VEGF-system in primary pulmonary angiosarcomas and haemangioendotheliomas: New potential therapeutic targets?
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Manipulation of the immune system by non-small cell lung cancer and possible therapeutic interference
No full textPulmonary carcinomas have developed mechanisms by which they escape the attack of immune cells. Immune checkpoint molecules programmed death 1 - programmed death ligand 1 (PD1-PDL1) and the cytotoxic T-lymphocyte antigen 4 system have gained attention. The expression of PDL1 by tumor cells causes immune tolerance, and further influences the microenvironment via orchestration by cytokines. Therapy with PDL1 antibodies could restore the cytotoxicity of T-lymphocytes towards tumor cells. Many patients will respond to this treatment. However, resistance mechanisms will counteract this therapy. New investigations have identified additional immune checkpoint inhibitors such as lymphocyte activation gene 3 and T cell immunoglobulin and mucin-domain containing-3. Tumor cells also induce tolerance by manipulating cells of the innate immune system. Macrophages are polarized to tumor-friendly M2, neutrophils into N2 types, and dendritic cells and myeloid suppressor cells are switched to assist tumor cells. Regulatory T cells enter the tumor microenvironment and signal tolerance to cytotoxic cells, inhibiting the influx of NK cells. Soluble mediators either released by tumor cells or cells of the tumor stroma induce immune tolerance, examples including tryptophan and indolamine dioxygenases, arginine and adenosine. Treatment options to counteract these molecules are currently being tested. The tumor stroma has been classified as immune-inflamed, immune-excluded, and immune-desert types. The latter might be switched to an inflamed type by induction of tertiary lymph follicles. Dendritic cells and macrophages normally phagocytose tumor antigens, but inhibitors of phagocytosis can block this. Interference with these molecules is another option for re-establishing the cytotoxic action of the immune system against tumor cells. In this review we will discuss these aspects with a special emphasis on non-small cell lung cancer
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