Coevolution of Solid Stress and Interstitial Fluid Pressure in Tumors During Progression: Implications for Vascular Collapse
| Autor: | Stylianopoulos, T., Martin, J. D., Snuderl, M., Mpekris, F., Jain, S. R., Jain, R. K. |
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| Přispěvatelé: | Stylianopoulos, T. [0000-0002-3093-1696] |
| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Pathology Hydrostatic pressure Vascular permeability Mice SCID animal cell Mice Models Neoplasms Extracellular fluid cancer cell Tumor article Tumor Burden tumor growth collapse Lymphatic system priority journal Oncology coevolution Disease Progression growth rate Perfusion Algorithms medicine.medical_specialty Physiological Biology Stress SCID Models Biological Article animal tissue Cell Line tissue pressure in vivo study vascular fragility blood vessel permeability male Stress Physiological In vivo Cell Line Tumor Hydrostatic Pressure medicine Humans Animals controlled study human mouse Cell Proliferation nonhuman hypoxia human cell animal model Extracellular Fluid Biological human tissue cell proliferation tumor volume Tumor progression Cancer cell mathematical model Neoplasm Transplantation |
| Zdroj: | Cancer research |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10–100 mmHg) – high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and fluid pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels. Cancer Res; 73(13); 3833–41. ©2013 AACR. |
| Databáze: | OpenAIRE |
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