engleski

Eta polycaprolactone (ε-PCL) implants appear to cause a partial differentiation of breast cancer lung metastasis in a murine model

Cells in every epithelium can be roughly divided in three compartments: stem cell (SC) compartment, transient amplifying cell (TA) compartment and mature or functional cell (FC) compartment. Maturation of stem cells is characterized epithelial stromal interaction and sequential maturational movement of stem cell’s progeny through those compartments. In this work we hypothesize that providing an artificial stroma, which murine breast cancer metastatic cells can infiltrate, will induce their differentiation. BALB/c female mice were injected with 106 isogenic 4T1 breast cancer cells labeled with GFP. After 20 days primary tumors were removed, and artificial ε-PCL implants were implanted on the contralateral side. After 10 more days mice were sacrificed and implants along with lung tissue were harvested. Mice were divided in four groups: tumor removal with sham implantation surgery (n=5), tumor removal with ε-PCL implant (n=5), tumor removal with VEGF enriched ε-PCL implant (n=7) and mice without tumor with VEGF enriched ε-PCL implant (n=3). Differentiational status of GFP+ cells was assessed by Ki67 and activated caspase 3 expression, thus dividing the population in SC like cells (Ki67+ aCasp3-), TA like cells (Ki67+ aCasp3+) and FC like cells (Ki67- aCasp3+/-) on flow cytometry. Lung metastatic load was reduced by 20% in mice with simple ε-PCL implant when compared to tumor bearing group with no implant (p<0.0001). Mice with VEGF enriched implants had 90% increase in lung metastatic load in comparison to tumor bearing mice with no implants (p<0.0001). Likewise, amount of GFP+ cells doubled in simple ε-PCL implant in comparison to VEGF enriched implants (p<0.0001). Differentiation wise, simple implants in comparison to sham group reduced the SC like cells by 25% and VEGF enriched implants reduced it further by another 20 % (i.e., 45% reduction in total) (p<0.0001). On the other hand, TA like cells were increased by amounts identical to SC-like cells decrease. Effects of both type of implants on FC like cells were minute. Both types of implants cause lung metastasis differentiation by shifting cancer cells from SC to TA compartment, leaving the FC compartment unaffected. VEGF enriched ε-PCL implants appear to decrease further migration of lung metastasis.

metastasis, breast cancer, differentiation, ε-PCL implant

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