title: Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model.
abstract: BACKGROUND
  Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d'orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth.
  
  
  METHODS
  Hypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs).
  
  
  RESULTS
  MSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors.
  
  
  CONCLUSIONS
  Our findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. lcalvarez@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. lcalvarez@mdanderson.org.
authors.forename: Lara
authors.initials: L
authors.lastname: Lacerda
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. bgdebeb@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. bgdebeb@mdanderson.org.
authors.forename: Bisrat G
authors.initials: BG
authors.lastname: Debeb
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. dlsmith2@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. dlsmith2@mdanderson.org.
authors.forename: Daniel
authors.initials: D
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. ralarson@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. ralarson@mdanderson.org.
authors.forename: Richard
authors.initials: R
authors.lastname: Larson
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. tnsolley@mdanderson.org.
authors.forename: Travis
authors.initials: T
authors.lastname: Solley
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. weixu@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. weixu@mdanderson.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. skrishna@mdanderson.org.|Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. skrishna@mdanderson.org.
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. yungong@mdanderson.org.|Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. yungong@mdanderson.org.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. lblevy@mdanderson.org.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Levy
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. tbuchhol@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. tbuchhol@mdanderson.org.
authors.forename: Thomas
authors.initials: T
authors.lastname: Buchholz
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. nueno@mdanderson.org.|Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. nueno@mdanderson.org.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. aklopp@mdanderson.org.
authors.forename: Ann
authors.initials: A
authors.lastname: Klopp
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. wwoodward@mdanderson.org.|Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. wwoodward@mdanderson.org.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D005260:Female; D064593:Heterografts; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D017077:Culture Media, Conditioned; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors