Adrenomedullin in Ovarian Cancer: Foe In Vitro and Friend In Vivo?
نویسندگان
چکیده
Stromal elements within a tumor interact with cancer cells to create a microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is an autocrine/paracrine factor produced by both stromal cells and cancer cells to create such a microenvironment. During differentiation of macrophages, ADM is produced in response to pro-inflammatory stimuli and hypoxia. In this study we investigated the role of ADM as a growth factor for ovarian cancer cells and as a modulator of macrophages. We also analyzed ADM expression levels in a retrospective clinical study using nanofluidic technology and assessment of ADM at the gene level in 220 ovarian cancer patients. To study the effects of ADM, ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant counterparts were used for proliferation assays, while monocytes from healthy donors were differentiated in vitro. ADM was a weak growth factor, as revealed by proliferation assays and cell cycle analysis. After culturing cancer cells under stressing conditions, such as serum starvation and/or hypoxia, ADM was found to be a survival factor in HEY but not in other cell lines. In macrophages, ADM showed activity on proliferation/differentiation, primarily in type 2 macrophages (M2). Unexpectedly, the clinical study revealed that high expression of ADM was linked to positive outcome and to cancer with low Ca125. In conclusion, although in vitro ADM was a potential factor in biological aggressiveness, this possibility was not confirmed in patients. Therefore, use of an ADM antagonist would be inappropriate in managing ovarian cancer patients.
منابع مشابه
The effects of adrenomedullin overexpression in breast tumor cells.
BACKGROUND Adrenomedullin is a secreted peptide hormone with multiple activities. Several reports have indicated that adrenomedullin may be involved in tumor survival, but this has not been directly shown. Here we evaluate the in vitro and in vivo effects of adrenomedullin overexpression in human breast cancer cells. METHODS The human breast cancer cell lines T47D and MCF7, both of which expr...
متن کاملI-12: Optimal Strategy toward Fertility Preservation: In Vivo and In Vitro Post-Thaw Options in Gamete, Embryo and Ovarian Tissue Cryostorage
Background: Oocyte, embryo and ovarian tissue cryopreservation are proposed for fertility preservation to cancer patients who hope to be mothers after getting rid of the disease. Materials and Methods: Embryo cryopreservation is not possible for unmarried single girls without sperm partner and oocyte retrieval is a long time procedure. Thus ovarian tissue cryopreservation is suggested for ferti...
متن کاملP-170: Animal Models of Human Artificial Ovary, Valuable Tools for Fertility Preservation in Cancer Patients
Background: With all the recent advances in cancer treatments, many young cancer patients find themselves facing the prospect of losing their fertility after aggressive chemotherapy or radiotherapy. Cryopreservation of ovarian cortical tissue has emerged as a potential option to restore fertility in these young women. Materials and Methods: Because autotransplantation of cryopreserved ovarian c...
متن کاملApocrine Metaplasia in Intraductal Papilloma with Foci of DCIS: A Friend or Foe?
Malignant papillary neoplasms of the breast comprise a number of microscopically distinct lesions, where apocrine metaplasia is commonly found in papillomas compared to other papillary lesions including papillary carcinomas. However, association of apocrine metaplasia in papilloma with Ductal Carcinoma in Situ (DCIS) is not very well defined. The lesions with apocrine metaplasia are not only di...
متن کامل