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Influence of preadipocyte-conditioned medium on the proliferation and invasive potential of breast cancer cell lines in vitro

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Autologous transplantation of adipose tissue into the breast is commonly performed in clinical practice, but its oncological safety has not been established.

Methods

We conducted an in vitro study to assess the influence of factors released by adipose-derived stem cells (ASCs), from multiple source tissues and harvested using different techniques, on proliferation and invasiveness of two breast cancer cell lines.

Results

Fat specimens of 66 donors (57 female, 9 male) were collected and 44 ASC cultures were established. ASC conditioning of the medium (CM) increased the proliferation of MCF-7 cells (178.4 ± 62.8%; P < 0.001), whereas MDA-MB321 proliferation was decreased (87.3 ± 15.3%; P = 0.032). We observed increased cell migration (174.0 ± 62.8%; P = 0.002), but not cell invasion (1.28 ± 0.51; P = 0.14) in MDA-MB231. Migration and invasion of MCF-7 cells were not affected by exposure to ASC-CM. For MCF-7 cell migration, lower BMI (< 25 kg/m2) was associated with increased migration, both in univariate (P = 0.015) and multivariate (P = 0.039) analyses. Regarding the cytokine secretome, proliferation of MCF-7 was positively correlated with levels of eotaxin 1 and insulin-like growth factor-binding protein 3 in the CM, and inversely correlated with levels of interleukin 1β and transforming growth factor β-3. In case of MDA-MB231, granulocyte colony-stimulating factor, angiogenin, eotaxin 1 and 3, neutrophil activating peptide 2, and neurotrophin-3 were positively correlated with proliferation.

Conclusions

We conclude that fat tissue transplantation increases proliferation and migration, but not invasion, of breast cancer cells. These findings are consistent with clinical data regarding the safety of autologous fat transplantation in breast cancer patients.

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Abbreviations

ASC:

Adipose-derived stem cells

BMI:

Body mass index

CM:

Conditioned medium/media

FCS:

Fetal calf serum

PBS:

Phosphate-buffered saline

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Acknowledgements

This work was supported by a grant from the Medical Faculty of the Ruhr-Universität Bochum (FoRUM F772N-2013).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Marien Hospital Herne, Ruhr-Universität Bochum, Hölkeskampring 40, Herne, Germany

    Anna Jablonka, Jan Scheich, Clemens B. Tempfer & Günther A. Rezniczek

  2. Department of Plastic Surgery and Burn Centre, BG University Hospital Bergmannsheil GmbH, Ruhr-Universität Bochum, Bochum, Germany

    Anna Jablonka, Frank Jacobsen, Tobias Hirsch & Marcus Lehnhardt

  3. Department of Plastic Surgery, Fachklinik Hornheide, Münster, Germany

    Tobias Hirsch

  4. Plastic and Anaesthetic Surgery Unit, Sana Kliniken Düsseldorf GmbH, Düsseldorf, Germany

    Mazen Hagouan

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Contributions

A. Jablonka: data collection, data analysis, manuscript writing. J. Scheich: data collection and management. F. Jacobsen: protocol development, manuscript editing. T. Hirsch: project development, manuscript editing. M. Hagouan: protocol development, data collection, manuscript editing. M. Lehnhardt: project development, manuscript editing. C.B. Tempfer: project development, manuscript writing. G.A. Rezniczek: project development, data analysis and management, manuscript writing.

Corresponding author

Correspondence to Günther A. Rezniczek.

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Data availability

Original data generated and analyzed during this study are available from the corresponding author on reasonable request.

Ethical approval

Collection of patient materials for this study was approved by the local ethics committees. All donors gave written informed consent. All experiments complied with German law.

Conflict of interest

All authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

404_2018_4910_MOESM1_ESM.pdf

Supplementary Fig. S1 (a and b) Heat maps of cytokine levels in a selection of 8 adipose-derived stem cell-conditioned media (#s 27, 28, 31, 36, 37, 39, 40, and 44) arranged by their effect on MCF-7 (a) and MDA-MB231 (b) cells (increasing proliferation, migration, and invasion; see Figs. 1 and 2). Proliferation, migration, and invasion values were correlated with cytokine levels (Spearman rank-order correlation). Arrows mark correlations with P < 0.1. *, P < 0.05; **, P < 0.01; ***, P < 0.001. Color range: green (≤ 0.25-fold row mean)—black (row mean)—red (≥ 4-fold row mean). (c) Bar graph showing the normalized results of the densitometric analyses (“signal”, arbitrary units) of the cytokine arrays (see Materials and Methods for details) (PDF 971 kb)

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Jablonka, A., Scheich, J., Jacobsen, F. et al. Influence of preadipocyte-conditioned medium on the proliferation and invasive potential of breast cancer cell lines in vitro. Arch Gynecol Obstet 298, 1159–1171 (2018). https://doi.org/10.1007/s00404-018-4910-6

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  • DOI: https://doi.org/10.1007/s00404-018-4910-6

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