Editors' ChoiceCancer

Studying the “Soil” for Metastatic “Seeds”

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Science Translational Medicine  05 Nov 2014:
Vol. 6, Issue 261, pp. 261ec189
DOI: 10.1126/scitranslmed.aaa1560

Metastatic spread has been famously likened to the planting of seeds (cancer cells) in suitable soil (distant organs) by the English surgeon Stephen Paget. He suggested that studying “properties of ‘the soils’ may reveal valuable insights into the metastatic peculiarities of cancer cases.” Unfortunately, until recently, such detailed study of the microenvironment of metastatic tumors has been hampered by difficulties in recovering the stromal component of the metastatic niche in vivo.

In a new study, Bersani et al. developed an implantable bioengineered scaffold from a gel seeded with human bone marrow stromal cells to mimic the three-dimensional microenvironment of the bone marrow, a frequent site for metastases from epithelial cancers. When these scaffolds were implanted under the skin of immunocompromised mice, they gradually lost the human cell component, which was replaced by mouse bone marrow stromal cells. The researchers then injected fluorescently labeled human breast and prostate cancer cells into these mice and observed the successful engraftment of circulating tumor cells into the bioengineered scaffolds.

At the molecular level, the authors used quantitative polymerase chain reaction to measure the expression of several known metastasis genes and compare the scaffolds harboring tumors to tumor-free scaffolds from the same mice. Interleukin-1β (IL-1β) was differentially expressed in cancer-seeded scaffolds, and immunohistochemical staining confirmed that the IL-1β originated from the stromal cells rather than the engrafted cancer cells.

This scaffold-based approach provides a new means of studying tumor microenvironments in vivo. The scaffolds can be explanted at different time points to monitor the evolution of the tumor microenvironment over time and to study the different cellular components of not just the “seeds” but also the “soil.”

F. Bersani et al., Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res. 10.1158/0008-5472.CAN-14-1809 (2014). [Full Text]

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