Inflammatory Breast Cancer: Factors Contributing to Dissemination

炎性乳腺癌：导致传播的因素

• 批准号: 8258693
• 负责人: BONNIE F SLOANE
• 金额: $ 5.75万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8258693
• 关键词: Accounting; African American; American; Architecture; Axilla; Biological Assay; Biological Markers; Biological Models; Blood; Breast Cancer Cell; Cancer Patient; Carcinoma; Cathepsins; Cathepsins B; Cell Surface Receptors; Cells; Coculture Techniques; Collaborations; Collagen Type IV; Colonic Neoplasms; Conditioned Culture Media; Cysteine; Cysteine Protease; Dermal; Diagnosis; Disease; Egypt; Embolism; Endocytosis; Engineering; Enhancers; Exhibits; Extracellular Matrix Proteins; Family; Fibroblasts; Functional Imaging; Future; Goals; Grant; Growth Factor; Immunodeficient Mouse; Implant; In Vitro; Incidence; Individual; Inflammatory; Intervention; Laboratories; Libraries; Life; Lymphatic; Lymphatic vessel; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Matrix Metalloproteinases; Modeling; Myoepithelial cell; Nature; Noninfiltrating Intraductal Carcinoma; Obstruction; Paraffin; Pathway interactions; Patients; Peptide Hydrolases; Phenotype; Play; Positive Axillary Lymph Node; Premalignant; Proteins; Proteolysis; Protocols documentation; Reagent; Reporting; Research; Research Personnel; Role; Screening procedure; Serine Protease; Specimen; Staging; Stromal Cells; Therapeutic; Therapeutic Intervention; Tumor Cell Invasion; United States; United States National Institutes of Health; Universities; Woman; Work; Xenograft procedure; breast lesion; cancer cell; cathepsin F; cathepsin V; cell type; chemokine; cytokine; implantation; improved; in vitro Model; in vivo; infiltrating duct carcinoma; inflammatory breast cancer; inhibitor/antagonist; macrophage; malignant breast neoplasm; malignant phenotype; monocyte; monolayer; neoplastic cell; neutralizing antibody; novel; novel therapeutics; parent grant; peripheral blood; preclinical study; programs; small hairpin RNA; tumor; tumor proteolysis; young woman

IBC is the most lethal form of primary breast cancer and disproportionately targets younger women. IBC accounts for <5% of all breast cancer cases in the United States, but its incidence is significantly higher among African-American women (10.1%). In Egypt, the incidence of IBC is reported to be from 5- 10% of all breast cancer cases and is on the rise. Extensive dermal lymphatic invasion and tumor emboli therein result in lymphatic obstruction that underlies the inflammatory nature of the disease. We have shown that macrophages infiltrate the IBC microenvironment, surround IBC emboli and are present in axillary blood of IBC patients. Our working hypothesis in this proposal is that IBC-associated macrophages play a crucial role in the formation of tumor emboli and dissemination of the cancer cells in the lymphatics, two of the phenotypic hallmarks of IBC. The Specific Aims of this FIRCA proposal are to: 1) Establish 3D cultures of IBC cells and a) assess invasive phenotype; b) determine expression/localization of putative IBC marker proteins; c) quantify expression of cytokines, chemokines and growth factors in conditioned media; and d) expression/secretion/activity of cysteine cathepsins; 2) Characterize monocyte/macrophage phenotype and content in tumor emboli, tumors, positive lymph nodes, axillary tributary blood and peripheral blood from IBC and non-IBC patients; 3) Isolate monocytes from IBC axillary tributary blood and peripheral blood and a) quantify expression of secreted cytokines, chemokines and growth factors, and b) expression/secretion/activity of cysteine cathepsins; 4) Immunostain paraffin blocks of IBC specimens for cell surface receptors of selected cytokines, chemokines and growth factors; and, 5) Establish 3D cocultures of IBC cells and monocytes isolated from IBC axillary tributary blood and peripheral blood and a) assess invasive phenotype; b) determine expression/localization of putative IBC marker proteins; c) quantify expression of cytokines, chemokines and growth factors in conditioned media; and d) expression/secretion/activity of cysteine cathepsins; and, e) immunostain cocultures for cell surface receptors identified in IBC specimens. Future directions will use the information obtained in Aims 1-5 to select cysteine cathepsins, cytokines, chemokines and growth factors that might be targeted to reduce the invasive phenotype of IBC. The aggressive manifestation of IBC in Egypt means that there is a pressing need to develop research programs that can be of immediate assistance to patients suffering from breast cancer. We anticipate that our results will contribute to the characterization of the pathobiological underpinnings of IBC, a prerequisite for prioritizing novel targets for therapeutic intervention. This research will be done primarily in Egypt at Cairo University in collaboration with Mona Mostafa Mohamed, as an extension of NIH Grant No. R01CA131990, 8-01-2008 to 5-31-2013.

IBC是原发性乳腺癌中最致命的一种，主要针对年轻女性。

项目成果

Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties.

• DOI: 10.1016/j.biocel.2013.11.015
• 发表时间: 2014-01
• 期刊: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
• 影响因子: 4
• 作者: Mohamed, Mona M.;El-Ghonaimy, Eslam A.;Nouh, Mohamed A.;Schneider, Robert J.;Sloane, Bonnie F.;El-Shinawi, Mohamed
• 通讯作者: El-Shinawi, Mohamed