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Angiogenesis and Lymphangiogenesis in IBC: Insights from a Genome-Wide Gene Expression Profiling Study

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Inflammatory Breast Cancer: An Update

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Abstract

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. Past molecular and morphological studies on cell lines, animal models and human tissue samples have unambiguously demonstrated that IBC is highly (lymph)angiogenic. Nevertheless, two vital questions remain unanswered: A. what is the role of the differential distribution of the molecular subtypes (particularly Luminal A) between IBC and nIBC in determining the observed difference in (lymph)angiogenesis and B. what are the exact molecular mechanisms that support angiogenesis in IBC? In this study, we aim to provide a clue for both questions by analyzing a gene expression data set of 137 IBC samples and 252 nIBC ­samples. In order to resolve the first question, a Gene Ontology analysis focusing on angiogenesis-related GO-terms was performed on the original data set and on the same data set after removing molecular subtype-specific variation in gene expression. In order to provide an answer to the second question, we identified angiogenesis-related IBC-specific genes that were subjected to Ingenuity Pathway Analysis. In addition, we focused part of our analysis on angiomiRs, microRNA-families that are known to regulate angiogenesis. Comparative analysis of all our data suggests that angiogenesis in IBC is not VEGFA-driven but is merely a consequence of a disturbed balance between proangiogenic and antiangiogenic factors, possibly involving PGF, TSP1 (THBS1) and the miR-221/-222-family. TSP1, a TGFβ-inducible gene that is upregulated in nIBC, is involved in the inhibition of angiogenesis, a process that also involves miR-221/-222. Therefore, we conclude that lack of inhibition of angiogenesis in IBC in conjunction with the increased expression of several angiogenesis-stimulating genes (PGF, mir-221/-222 gene targets) results in increased levels of angiogenesis-related histomorphometrical parameters in IBC.

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Author information

Authors and Affiliations

  1. Translational Cancer Research Unit, Oncology Center, General Hospital Sint-Augustinus, Wilrijk, Belgium

    Peter B. Vermeulen, Gert Van den Eynden, Luc Y. Dirix & Steven J. Van Laere

  2. World IBC Consortium, Houston, USA

    Peter B. Vermeulen, Gert Van den Eynden, Pascal Finetti, Daniel Birnbaum, Naoto T. Ueno M.D., Ph.D., F.A.C.P., Patrice Viens, François Bertucci & Luc Y. Dirix

  3. Department of Oncology, Catholic University Leuven, Leuven, Belgium

    Steven J. Van Laere

  4. Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France

    Pascal Finetti, Daniel Birnbaum, Patrice Viens & François Bertucci

  5. Morgan Welch Inflammatory Breast Cancer Program and Clinic, Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Unit 1354, Holcombe Blvd. 1515, Houston, TX, USA

    Naoto T. Ueno M.D., Ph.D., F.A.C.P.

Authors
  1. Peter B. Vermeulen
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  2. Gert Van den Eynden
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  3. Pascal Finetti
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  4. Daniel Birnbaum
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  5. Naoto T. Ueno M.D., Ph.D., F.A.C.P.
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  6. Patrice Viens
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  7. François Bertucci
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  8. Luc Y. Dirix
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  9. Steven J. Van Laere
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Corresponding author

Correspondence to Peter B. Vermeulen .

Editor information

Editors and Affiliations

  1. MD Anderson Cancer Center, Dept. Breast Medical Oncology, University of Texas, Holcombe Blvd. 1515, Houston, 77030-4095, Texas, USA

    Naoto T. Ueno

  2. Fox Chase Cancer Center, Cottman Avenue; Room C315 333, Philadelphia, 19111, Pennsylvania, USA

    Massimo Cristofanilli

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Vermeulen, P.B. et al. (2012). Angiogenesis and Lymphangiogenesis in IBC: Insights from a Genome-Wide Gene Expression Profiling Study. In: Ueno, N., Cristofanilli, M. (eds) Inflammatory Breast Cancer: An Update. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3907-9_18

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