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A New Model for Lymphatic Metastasis: Development of a Variant of the MDA-MB-468 Human Breast Cancer Cell Line that Aggressively Metastasizes to Lymph Nodes

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Abstract

Breast cancer often spreads from the primary tumor to regional lymph nodes. Lymph node status provides clinically important information for making treatment decisions. Spread via lymphatics is also important for the biology of breast cancer, as tumor cells in lymph nodes may provide a reservoir of cells leading to distant, lethal metastases. Improved understanding of the biology of lymphatic spread thus is important for improved breast cancer survival. Advances towards understanding the interactions between tumors cells and lymphatic vessels have in part been limited by the lack of suitable cell lines and experimental models. We have addressed this need by developing a new model of lymphatic metastasis. Here we describe the establishment of 468LN cells, a variant of the MDA-MB-468 human breast adenocarcinoma cell line, which produces extensive lymph node metastasis following orthotopic injection of nude mice. 468LN cells are also more aggressive in vitro, produce more osteopontin and express different surface integrins compared to the parent line. The dramatic in vitro and in vivo phenotypic and molecular differences of 468LN and parental 468GFP cells make this pair of cell lines a unique model for the specific study of lymph node metastasis of breast cancer.

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Abbreviations

ECM:

extracellular matrix

EGFR:

epidermal growth factor receptor

GFP:

green fluorescent protein

mfp:

mammary fat pad

OPN:

osteopontin

VCAM-1:

vascular cell adhesion molecule

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Authors and Affiliations

  1. London Regional Cancer Program, 790 Commissioners Road East, Ontario, N6A 4L6, London, Canada

    Sharon A. Vantyghem, Alison L. Allan, Carl O. Postenka, Waleed Al-Katib, Alan B. Tuck & Ann F. Chambers

  2. Department of Pathology, University of Western Ontario, Ontario, London, Canada

    Sharon A. Vantyghem, Alan B. Tuck & Ann F. Chambers

  3. Department of Oncology, University of Western Ontario, Ontario, London, Canada

    Sharon A. Vantyghem, Alison L. Allan, Alan B. Tuck & Ann F. Chambers

  4. London Health Sciences Centre, Ontario, London, Canada

    Michael Keeney & Alan B. Tuck

  5. Lawson Health Research Institute, Ontario, London, Canada

    Michael Keeney & Ann F. Chambers

Authors
  1. Sharon A. Vantyghem
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  2. Alison L. Allan
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  3. Carl O. Postenka
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  4. Waleed Al-Katib
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  5. Michael Keeney
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  6. Alan B. Tuck
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  7. Ann F. Chambers
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Correspondence to Ann F. Chambers.

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Vantyghem, S.A., Allan, A.L., Postenka, C.O. et al. A New Model for Lymphatic Metastasis: Development of a Variant of the MDA-MB-468 Human Breast Cancer Cell Line that Aggressively Metastasizes to Lymph Nodes. Clin Exp Metastasis 22, 351–361 (2005). https://doi.org/10.1007/s10585-005-0745-1

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  • DOI: https://doi.org/10.1007/s10585-005-0745-1

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