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Elevated physiologic tumor pressure promotes proliferation and chemosensitivity in human osteosarcoma
Saminathan S Nathan1, Gene R DiResta, Jorge E Casas-Ganem
1Orthopaedic Surgery Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275A York Avenue, New York, NY 10021, USA.
Summary
Elevated interstitial fluid pressure in osteosarcoma increases cell proliferation and enhances sensitivity to chemotherapy drugs like cisplatin and doxorubicin, suggesting pressure influences treatment outcomes.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Biology
Background:
- Tumor interstitial fluid pressure (TIFP) is a poorly understood factor in cancer progression.
- High TIFP may influence tumor physiology and response to therapy.
Purpose of the Study:
- To investigate the impact of elevated interstitial fluid pressure on osteosarcoma physiology.
- To determine the effect of interstitial fluid pressure on osteosarcoma chemosensitivity.
Main Methods:
- Assessed TIFP and blood flow in high-grade osteosarcoma patients during biopsy.
- Correlated TIFP with patient survival and chemotherapy-induced tumor necrosis.
- Evaluated osteosarcoma cell lines in a novel high-pressure in vitro system for proliferation and chemosensitivity.
Main Results:
- In vivo, elevated TIFP (mean 35.2 mmHg) in osteosarcomas correlated with increased chemotherapy-associated necrosis and longer survival.
- In vitro, pressurized osteosarcoma cells showed increased proliferation, with more cells in S phase and elevated E2F-1/E2F-4 transcription factors.
- Pressurized cells exhibited significantly increased sensitivity to cisplatin and doxorubicin.
Conclusions:
- Osteosarcoma cells under elevated interstitial fluid pressure display heightened regenerative activity compared to standard culture conditions.
- Tumor interstitial fluid pressure variations can significantly modulate the effectiveness of chemotherapy.