Understanding the biology of inflammatory breast cancer (IBC) cutaneous metastasis and the role of TGFβ
Date
2018
Authors
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Publisher
University of Delaware
Abstract
Inflammatory breast cancer (IBC) is a highly aggressive form of locally advanced breast cancer with unique molecular and phenotypic properties (Dawood, Merajver et al. 2011, Dawood and Valero 2012, Joglekar and van Golen 2012). Cutaneous metastases from internal cancers are relatively rare, occurring at a rate of 0.7-9.0% (Martin 1997). IBC cutaneous metastasis is associated with chest wall recurrences, significantly decreasing the quality of life and survival (Cristofanilli, Valero et al. 2007). Although significantly different in many aspects, IBC and melanoma share a number of similarities in disease presentation and progression. Both spread via dermal lymphatics, form intralymphatic emboli and have a propensity to form cutaneous metastases (Fidler 1990, Leiter, Meier et al. 2004, Rose, Christos et al. 2011). Thus, new leads for studying cutaneous metastasis can be gathered from the melanoma literature. In melanoma, there were several studies done on radiation and TGFβ to demonstrate the role of TGFβ on the etiology of melanoma cutaneous metastasis (Schmid, Itin et al. 1995, Perrot, Javelaud et al. 2013). There were no studies done to date to understand the biology of inflammatory breast cancer cutaneous metastasis in relation to radiation and the role of TGFβ. Here my doctoral project is primarily focusing on the influence of radiation in IBC cutaneous metastasis and the role of TGFβ. I radiated normal human fibroblast cells with different doses of radiation and used the conditioned media to see the invasiveness of the IBC cells (KPL4 and SUM149) and compared them with the conventional breast cancer cells (MDA-MB-231). I observed that the IBC cell invasion is significantly higher with higher doses of radiation. Also there is higher expression of TGFβ-2 with higher (5 Gy) dose of radiation. I also used RNA sequencing to identify the molecular signature profile of IBC and non-IBC cells which may lead to the therapeutic treatment of IBC cutaneous metastasis.
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Keywords
Biological sciences, Cutaneous metastasis, Inflammatory breast cancer, TGFbeta