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Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High‐Metastatic Variant of Human Triple‐Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models
Author(s) -
Yano Shuya,
Takehara Kiyoto,
Tazawa Hiroshi,
Kishimoto Hiroyuki,
Kagawa Shunsuke,
Bouvet Michael,
Fujiwara Toshiyoshi,
Hoffman Robert M.
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25735
Subject(s) - medicine , triple negative breast cancer , lymph , lymph node , lymphatic system , breast cancer , malignancy , metastasis , cancer , pathology , metastatic breast cancer , primary tumor , cancer research , ca15 3 , mammary gland
We previously developed and characterized a highly invasive and metastatic triple‐negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA‐MB‐231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re‐implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high‐metastatic MDA‐MB‐231H‐RFP cells produced significantly larger subcutaneous tumors compared with parental MDA‐MB‐231 cells in nude mice. Extensive lymphatic trafficking by high‐metastatic MDA‐MB‐231 cells was also observed. High‐metastatic MDA‐MB‐231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA‐MB‐231 high‐metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non‐surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559–569, 2017. © 2016 Wiley Periodicals, Inc.