adipoSIGHT in Therapeutic Response: Consequences in Osteosarcoma Treatment

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells
engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and
the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement
of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo
(osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study
to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell
tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell–cell
interaction is investigated by means of E-cadherin expression. Comparatively high expression of Ecadherin
and compact organization is observed in heterotypic tumorspheres (Saos 2–ASCs) compared
to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into
the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic.
In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are
overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively
repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points
toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and
warrants further investigation.