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Stem Cells Transl Med. 2018 Jan;7(1):125-134. doi: 10.1002/sctm.17-0062.

An Animal Model of Local Breast Cancer Recurrence in the Setting of Autologous Fat Grafting for Breast Reconstruction.

Author information

1
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
Department of Breast Surgery, Shiga General Hospital, Moriyama, Shiga, Japan.
3
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
4
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
5
Department of Medicine, University of Pittsburgh Cancer Center, Pittsburgh, Pennsylvania, USA.
6
Department of Cardiothoracic Surgery, University of Pittsburgh Cancer Center, Pittsburgh, Pennsylvania, USA.

Abstract

Autologous fat grafting after breast cancer surgery is commonly performed, but concerns about oncologic risk remain. To model the interaction between fat grafting and breast cancer cells, two approaches were employed. In the first approach, graded numbers of viable MDA-MB-231 or BT-474 cells were admixed directly into human fat grafts and injected subcutaneously into immune-deficient mice to determine if the healing graft is a supportive environment for the tumor. In the second approach, graded doses of MDA-MB-231 cells were suspended in Matrigel and injected into the mammary fat pads of mice. Two weeks after the tumor cells engrafted, 100 μL of human adipose tissue was grafted into the same site. Histologically, MDA-MB-231 cells seeded within fat grafts were observed and stained positive for human-specific pan-cytokeratin and Ki67. The BT-474 cells failed to survive when seeded within fat grafts at any dose. In the second approach, MDA-MB-231 cells had a strong trend toward lower Ki67 staining at all doses. Regression analysis on all groups with fat grafts and MDA-MB-231 revealed fat tissue was associated with lower cancer cell Ki67 staining. Healing fat grafts do not support the epithelial BT-474 cell growth, and support the mesenchymal MDA-MB-231 cell growth only at doses ten times greater than in Matrigel controls. Moreover, fat grafts in association with MDA-MB-231 cancer cells already present in the wound resulted in decreased tumor proliferation and increased fibrosis. These findings suggest that clinical fat grafting does not induce breast cancer cell growth, and may even have a suppressive effect. Stem Cells Translational Medicine 2018;7:125-134.

KEYWORDS:

Animal model; Autologous fat grafting; BT-474; Breast cancer local recurrence; MDA-MB-231; NOD scid gamma mice

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