Related Experiment Video
Updated: Oct 30, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
adipoSIGHT in Therapeutic Response: Consequences in Osteosarcoma Treatment
Banani Kundu1,2, Virginia Brancato1,2, Joaquim Oliveira1,2
13B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, Portugal.
Abstract:
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 E-cadherin 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.
Insights
Co-culturing osteosarcoma cells with human adipose-derived stem cells (ASCs) created tumorspheres that resisted chemotherapy. This interaction suggests potential oncological risks with ASC-based therapies in cancer patients.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Regenerative Medicine
Background:
- Chemotherapeutic resistance is a significant challenge in cancer treatment, leading to disease recurrence and metastasis.
- Cancer stem cells and stromal interactions, including those with stem cells, influence treatment efficacy.
- Osteosarcoma, a bone cancer, presents challenges due to its complex cellular microenvironment.
Purpose of the Study:
- To investigate the therapeutic response of co-cultured osteosarcoma (Saos 2) and human adipose-derived stem cells (ASCs).
- To analyze cell-cell interactions and drug resistance mechanisms within tumorspheres formed by Saos 2 and ASCs.
- To assess the potential oncological risks associated with using ASCs in cancer patients.
Main Methods:
- Co-culture of Saos 2 cells and ASCs on a nonadherent, concave surface to form tumorspheres.
- Real-time microscopic monitoring of cell arrangement using cell tracker dyes.
- Investigation of cell-cell interaction via E-cadherin expression analysis.
- Assessment of doxorubicin infiltration and gene expression (SOX2, OCT4, CD44) post-chemotherapy.
Main Results:
- Heterotypic tumorspheres (Saos 2-ASCs) exhibited higher E-cadherin expression and compact organization compared to homotypic tumorspheres.
- Limited doxorubicin infiltration was observed in heterotypic tumorspheres, conferring protection against chemotherapy.
- Genes associated with drug resistance (SOX2, OCT4, CD44) were overexpressed in heterotypic tumorspheres after chemotherapy.
Conclusions:
- The interaction between Saos 2 cells and ASCs enhances chemoresistance by forming a protective barrier and upregulating drug resistance genes.
- ASCs may contribute to chemotherapy resistance in osteosarcoma.
- The findings highlight potential oncological risks of ASC-based regenerative therapies in cancer patients, necessitating further research.
