Magali Castells

Publications (3)11.35 Total impact

• Article: Ovarian ascites-derived Hospicells promote angiogenesis via activation of macrophages.

  Magali Castells, Benoît Thibault, Eliane Mery, Muriel Golzio, Marlene Pasquet, Isabelle Hennebelle, Philippe Bourin, Massoud Mirshahi, Jean Pierre Delord, Denis Querleu, Bettina Couderc
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  ABSTRACT: Within the microenvironment, Carcinoma-associated mesenchymal stem cells (Hospicells) are able to influence ovarian tumor development via, among others, the facilitation of angiogenesis in the tumor site allowing an accelerated tumor growth. We demonstrate the presence of a chemotactism between endothelial cells and Hospicells, and a cell line specific increased secretion of pro-angiogenic cytokines such as IL-6, IL-8 and VEGF from ovarian adenocarcinoma cells. Hospicells are also able to attract and activate macrophages to a M2 phenotype and allow them to secrete a huge quantity of pro-angiogenic cytokines, favorable to tumor progression of all the associated ovarian adenocarcinoma cells tested.
  Cancer letters 07/2012; 326(1):59-68. · 4.86 Impact Factor
• Article: Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death.

  Magali Castells, Benoît Thibault, Jean-Pierre Delord, Bettina Couderc
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  ABSTRACT: Tumor development principally occurs following the accumulation of genetic and epigenetic alterations in tumor cells. These changes pave the way for the transformation of chemosensitive cells to chemoresistant ones by influencing the uptake, metabolism, or export of drugs at the cellular level. Numerous reports have revealed the complexity of tumors and their microenvironment with tumor cells located within a heterogeneous population of stromal cells. These stromal cells (fibroblasts, endothelial or mesothelial cells, adipocytes or adipose tissue-derived stromal cells, immune cells and bone marrow-derived stem cells) could be involved in the chemoresistance that is acquired by tumor cells via several mechanisms: (i) cell-cell and cell-matrix interactions influencing the cancer cell sensitivity to apoptosis; (ii) local release of soluble factors promoting survival and tumor growth (crosstalk between stromal and tumor cells); (iii) direct cell-cell interactions with tumor cells (crosstalk or oncologic trogocytosis); (iv) generation of specific niches within the tumor microenvironment that facilitate the acquisition of drug resistance; or (v) conversion of the cancer cells to cancer-initiating cells or cancer stem cells. This review will focus on the implication of each member of the heterogeneous population of stromal cells in conferring resistance to cytotoxins and physiological mediators of cell death.
  International Journal of Molecular Sciences 01/2012; 13(8):9545-71. · 2.60 Impact Factor
• Article: Intraoperative fluorescence imaging of peritoneal dissemination of ovarian carcinomas. A preclinical study.

  Eliane Mery, Eva Jouve, Stephanie Guillermet, Maxime Bourgognon, Magali Castells, Muriel Golzio, Philippe Rizo, Jean Pierre Delord, Denis Querleu, Bettina Couderc
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  ABSTRACT: Improvement of the management and outcome of ovarian cancers may require intraoperative detection and therapeutic intervention to treat minimal residual disease after complete surgery. The aim of this study was to validate the importance of fluorescence in the peroperative detection of human ovarian adenocarcinoma cells and to determine its efficiency in detecting infra millimetric tumor metastases. A fluorescent RAFT-(cRGD)₄ tracer molecule (AngioStamp®) was used. The tracer is based on a biomarker, which has a very high affinity for the α(v)β₃ integrin, which is overexpressed in a large ratio of cancer cells and neovessel endothelial cells during angiogenesis. Infrared fluorescence was visualized with Fluobeam®, an open fluorescent imaging system that could potentially be used in peroperative conditions in the future. This novel technique allowed the specific detection of residual tumor deposits and inframillimetric metastases, smaller than 500μm, which were resected under fluorescent guidance. AngioStamp® was able to detect all types of cell lines, derived from human ovarian adenocarcinomas, before or after chemotherapy treatment in animals. The effectiveness of AngioStamp® for the detection of various human ovarian adenocarcinomas was assessed on 10 different fragments of tumor, implanted subcutaneously in nude mice. All implanted tumor fragments were visualized by AngioStamp®. The high rate of recurrence after apparently complete surgery and/or complete clinical response to chemotherapy implies that most patients have undetected minimal residual disease. Novel techniques such as laparoscopic or laparotomic fluorescence may prove to be crucial in reassessing the definition of primary outcome in ovarian cancer management.
  Gynecologic Oncology 04/2011; 122(1):155-62. · 3.89 Impact Factor