title: Inflammatory breast cancer (IBC): clues for targeted therapies.
abstract: Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast cancer characterized by rapid proliferation, early metastatic development and poor prognosis. Since there are few preclinical models of IBC, there is a general lack of understanding of the complexity of the disease. Recently, we have developed a new model of IBC derived from the pleural effusion of a woman with metastatic secondary IBC. FC-IBC02 cells are triple negative and form clusters (mammospheres) in suspension that are strongly positive for E-cadherin, β-catenin and TSPAN24, all adhesion molecules that play an important role in cell migration and invasion. FC-IBC02 cells expressed stem cell markers and some, but not all of the characteristics of cells undergoing epithelial mesenchymal transition (EMT). Breast tumor FC-IBC02 xenografts developed quickly in SCID mice with the presence of tumor emboli and the development of lymph node and lung metastases. Remarkably, FC-IBC02 cells were able to produce brain metastasis in mice on intracardiac or intraperitoneal injections. Genomic studies of FC-IBC02 and other IBC cell lines showed that IBC cells had important amplification of 8q24 where MYC, ATAD2 and the focal adhesion kinase FAK1 are located. MYC and ATAD2 showed between 2.5 and 7 copies in IBC cells. FAK1, which plays important roles in anoikis resistance and tumor metastasis, showed 6-4 copies in IBC cells. Also, CD44 was amplified in triple-negative IBC cells (10-3 copies). Additionally, FC-IBC02 showed amplification of ALK and NOTCH3. These results indicate that MYC, ATAD2, CD44, NOTCH3, ALK and/or FAK1 may be used as potential targeted therapies against IBC.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Sandra.Fernandez@jefferson.edu
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Fernandez
authors.forename: Fredika M
authors.initials: FM
authors.lastname: Robertson
authors.forename: Jianming
authors.initials: J
authors.lastname: Pei
authors.forename: Lucy
authors.initials: L
authors.lastname: Aburto-Chumpitaz
authors.forename: Zhaomei
authors.initials: Z
authors.lastname: Mu
authors.forename: Khoi
authors.initials: K
authors.lastname: Chu
authors.forename: R K
authors.initials: RK
authors.lastname: Alpaugh
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Ye
authors.forename: Kathy Q
authors.initials: KQ
authors.lastname: Cai
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Boley
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: Karthik
authors.initials: K
authors.lastname: Devarajan
authors.forename: Sankar
authors.initials: S
authors.lastname: Addya
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary; D015704:CD4 Antigens / Q000235:genetics; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D015704:CD4 Antigens; D015820:Cadherins; D004268:DNA-Binding Proteins; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; C496050:PTK2 protein, human; C103547:PTK2B protein, human; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities