Abstract P1-12-02: Growth hormone and prolactin influences mammary epithelial and stromal interactions in early parity induced protection against breast cancer

Abstract

Abstract Introduction: Early pregnancy has been shown to decrease the life-time risk of mammary cancer. Further, systemic alterations in circulating levels of growth hormone (GH) and prolactin (PRL) have been associated with the decreased risk. GH and PRL have been shown to affect the mammary stroma and epithelium. Carcinogenesis is a multistep process and there are several ways in which the host environment can affect progression of initiated cells to neoplasia. During normal and tumor development complex interactions occur between epithelial cells and stromal cells in the tissue microenvironment. These epithelial-stromal interactions in the microenvironment play a crucial role in the progression of mammary tumors. Determining the epithelial-stromal regulation by GH and PRL in the mammary gland of early parous rats is expected to improve our understanding of the dynamics of the epithelium and stromal interactions in mammary carcinogenesis. Materials and Methods: The inguinal mammary fat pad was cleared of the host mammary gland in 3-4-week-old female Lewis rats. One group (n=20) of rats were exposed to MNU at 7 weeks of age, and another group (n=20) of rats were not exposed to MNU. A subset (n=10) of rats from each of these experimental groups were mated at 9 weeks and allowed to go through a full-term pregnancy. The mothers were allowed to lactate for 3 weeks and weaned. All animals were terminated 6 weeks post-weaning. Mammary epithelial cells (MECs) were isolated using a standard collagenase cell dissociation procedure. The isolated MECs (5 × 105) were transplanted into the gland-free fat pads of respective hosts (n=30). MECs isolated from control and carcinogen treated age-matched nulliparous (AMNP) rats were transplanted into the gland-free fat pads of parous hosts and similarly MECs from control and carcinogen treated parous were transplanted into gland-free fats pads of AMNP hosts. In brief, we studied the following groups to understand the influence of early parity on epithelial-stromal interactions involved in mammary carcinogenesis: 1) carcinogen treated MECs from AMNP rats was transplanted into untreated parous rats; 2) carcinogen treated MECs from parous rats was transplanted into untreated AMNP rats; 3) untreated MECs from AMNP rats was transplanted into carcinogen treated parous rats and 4) untreated MECs from parous rats was transplanted into carcinogen treated AMNP rats. In another experiment, we treated a subset of the above mentioned groups with GH or PRL (n=10). Mammary carcinogenesis was monitored weekly for incidence, multiplicity, and latency. The cancerous nature of the palpable tumors was confirmed by histopathological analysis. Results: Our results demonstrate that when MECs from AMNP rats were transplanted to parous hosts they did not grow further to make palpable cancers. In contrast when MECs from parous rats were transplanted to AMNP they formed palpable cancers. Further, administration of GH or PRL increased carcinogenesis in parous rats. Conclusion: These findings indicate that the epithelial stromal interactions are important for mammary carcinogenesis and they are influenced significantly by GH and PRL. Citation Format: Ramadevi Subramani, Adriana Galvez, Diego Pedroza, Alejandro Bencomo, Madeline Dixon, Rajkumar Lakshmanaswamy. Growth hormone and prolactin influences mammary epithelial and stromal interactions in early parity induced protection against breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-12-02.