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.
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.
AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California San Diego, San Diego, California.|Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shuya
S
Yano
AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California San Diego, San Diego, California.|Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kiyoto
K
Takehara
Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
Hiroshi
H
Tazawa
AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California San Diego, San Diego, California.|Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hiroyuki
H
Kishimoto
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shunsuke
S
Kagawa
Department of Surgery, University of California San Diego, San Diego, California.
Michael
M
Bouvet
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Toshiyoshi
T
Fujiwara
AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California San Diego, San Diego, California.
Robert M
RM
Hoffman
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002465:Cell Movement; D005260:Female; D064593:Heterografts; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
BREAST CANCER; HIGH-METASTATIC VARIANT; IMAGING; LYMPHATIC TRAFFICKING; MDA-MB-231; NUDE MICE; ORTHOTOPIC; RECURRENCE; RED FLUORESCENT PROTEIN; SURGICAL RESECTION; TRIPLE NEGATIVE