Abstract A07: A new perspective on cancer: Tumor initiation, failure of treatments, and metastasis
Authors: Shahriyari Leili 
Published: May 2019

Abstract
Here, we look at inflammatory cancers from a new perspective. We investigate the process of tumor initiation and progression in the site of chronic inflammation. We argue that inflammatory carcinomas are initiated at the sites of chronic inflammation because chronic inflammation might cause cells to become adapted to the wound healing process. For example, immune cells might be adapted to send signals of proliferation and/or angiogenesis, and tissue cells might be adapted to proliferation (like inactivation of tumor suppressor genes). We propose that despite the common belief that metastases are the result of tumor circulating cells, metastases could be the result of wound healing process by adapted immune cells in the sites of inflammation. If there are adapted immune cells, then the new site of inflammation might recruit these adapted immune cells. The adapted immune cells would send more inflammatory signals than normal immune cells; therefore a new tumor would be generated. Note that immune cells are very active in lung, liver, and bone, which are the common metastasis sites for inflammatory cancers. There is also another possible process; the new site of inflammation recruits activated platelets. The activated platelets travel between sites of inflammation, which includes the site of inflammatory carcinoma. Tumor cells can link to adhesion receptors on platelets, so they can travel with activated platelets to the new site of inflammation. These activated platelets will start wound healing process in this site, which now includes some tumor cells. The tumor cells would respond to the wound healing signals more strongly than normal cells, thus new tumor would initiate in this site of inflammation. If this hypothesis is true, then chemotherapy could facilitate the process of metastasis for inflammatory carcinomas. As the result of chemotherapy, the DAMP protein, high mobility group box 1, is released and triggers the immune response. From this hypothesis, we may also conclude that any treatments generating necrotic cells in the tumor microenvironment, which is orchestrated by adapted immune, stromal, and/or epithelial cells may not be a good solution. Necrotic cells in the tumor microenvironment activate the immune system to initiate wound healing process. If the tumor includes adapted tissue or/and adapted immune cells, then these adapted cells start the wound healing process in the tumor microenvironment. Adapted activated immune cells send more signals of proliferation or/and angiogenesis than normal cells. Furthermore, if there were adapted tissue cells, then in response to these signals, adapted cells would divide at a much higher rate than normal cells. Thus, not only would the tumor come back after the treatment, but also its growth would be more aggressive.
We also suggest that understanding and comparing the wound healing process in the normal and tumor microenvironments is necessary to understand inflammatory cancers and their mechanism.
Citation Format: Leili Shahriyari. A new perspective on cancer: Tumor initiation, failure of treatments, and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A07.