by ecancer reporter Clare Sansom

Breast reconstruction following cancer surgery often involves a process known as autologous lipotransfer, in which fatty adipose tissue from another part of the patient’s body is used to replace the lost breast tissue.

Adipose tissue from mice and other mammals has recently been reported to contain endothelial progenitor cells (EPCs), stem-like cells with the ability to differentiate into the lining of blood vessels. These cells, which are found in bone marrow, are involved in the angiogenesis that is necessary for tumour growth and at least some pre-clinical models of tumour growth seem to depend on these cells.

Francesco Bertolini and his colleagues at the European Institute of Oncology, Milan, Italy have now investigated samples of human bone marrow and white adipose tissue (WAS) for the presence of endothelial progenitor cells. The white adipose tissue was taken from samples used in autologous lipotransfer for breast reconstruction following breast cancer surgery.

Both tissues were found using flow cytometry to contain fairly large numbers of cells that express the CD45 and CD34 antigens (CD34⁺ cells) and that can be identified as endothelial progenitor cells. The concentration of EPCs in the adipose tissue was many times greater than that in the bone marrow. Older breast cancer patients and patients with a higher body mass index had higher overall numbers of these cells in their adipose tissue.

The EPCs from the two tissue types were purified and their gene expression profiles compared using Affymetrix microarrays.  Compared to the bone marrow derived cells, the adipose tissue derived CD34⁺ cells expressed higher levels of a number of genes that have been associated with angiogenesis (e.g. VEGFR-1 and -2); adipogenesis; and endothelial differentiation.

The WAS-derived cells also expressed higher levels of the gene FAP-alpha, a suppressor of anti-tumour immunity. Genes associated with stemness were expressed at similar levels in both cell populations.

The researchers cultured the WAT-derived CD34⁺ cells in vitro in endothelial-differentiation media and found that they could generate both mature endothelial cells and endothelial capillary tubes. They then used a mouse model of breast cancer to investigate the role of these cells in tumour growth and metastasis.

The mammary fat pads of female immunodeficient mice were injected with triple negative breast cancer cells; CD34⁺ cells; or both cell types at the same time. The cancer cells generated tumours in the fat pads with or without the CD34⁺ cells, but co-injection with these cells increased tumour growth.

Tumours in this mouse model metastasise to the lungs after about 70 days, and co-injecting the tumour cells with CD34⁺ cells increased the number of these metastases. Cells derived from white adipose tissue that did not express these antigens (CD34^- cells) did not promote tumour growth or metastasis.

When purified EPCs were injected into the mammary fat pads of the same mice after small tumours had been removed by surgery, CD34⁺ but not CD34^- cells promoted metastases to the lungs and the axillary nodes.

Finally, the researchers showed using confocal microscopy that endothelial cells derived from CD34⁺ cells could be found lining the lumen of tumour blood vessels, an effect that has not been observed with bone marrow derived EPCs.

Taken together, these results show that there are cells in the adipose tissue used in breast reconstruction surgery following breast cancer treatment promote cancer progression and metastasis. This may have important implications for the development of this technique.

Reference

Martin-Padura, I., Gregato, G., Marighetti, M. and 9 others (2011). The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Research, published online ahead of print 3 November 2011.

doi: 10.1158/0008-5472.CAN-11-1739