Modeling Physical Forces Experienced by Cancer and Stromal Cells Within Different Organ-Specific Tumor Tissue.

Mechanical force exerted on cancer cells by their microenvironment have been reported to drive cells toward invasive phenotypes by altering cells' motility, proliferation, and apoptosis. These mechanical forces include compressive, tensile, hydrostatic, and shear forces. The importance of forces is then hypothesized to be an alteration of cancer cells' and their microenvironment's biophysical properties as the indicator of a tumor's malignancy state. Our objective is to investigate and quantify the correlation between a tumor's malignancy state and forces experienced by the cancer cells and components of the microenvironment. In this study, we have developed a multicomponent, three-dimensional model of tumor tissue consisting of a cancer cell surrounded by fibroblasts and extracellular matrix (ECM). Our results on three different organs including breast, kidney, and pancreas show that: A) the stresses within tumor tissue are impacted by the organ specific ECM's biophysical properties, B) more invasive cancer cells experience higher stresses, C) in pancreas which has a softer ECM (Young modulus of 1.0 kPa) and stiffer cancer cells (Young modulus of 2.4 kPa and 1.7 kPa) than breast and kidney, cancer cells experienced significantly higher stresses, D) cancer cells in contact with ECM experienced higher stresses compared to cells surrounded by fibroblasts but the area of tumor stroma experiencing high stresses has a maximum length of 40 µm when the cancer cell is surrounded by fibroblasts and 12 µm for when the cancer cell is in vicinity of ECM. This study serves as an important first step in understanding of how the stresses experienced by cancer cells, fibroblasts, and ECM are associated with malignancy states of cancer cells in different organs. The quantification of forces exerted on cancer cells by different organ-specific ECM and at different stages of malignancy will help, first to develop theranostic strategies, second to predict accurately which tumors will become highly malignant, and third to establish accurate criteria controlling the progression of cancer cells malignancy. Furthermore, our in silico model of tumor tissue can yield critical, useful information for guiding ex vivo or in vitro experiments, narrowing down variables to be investigated, understanding what factors could be impacting cancer treatments or even biomarkers to be looking for.

Association of Hypertension and Organ-Specific Cancer: A Meta-Analysis.

Hypertension and cancer are two of the leading global causes of death. Hypertension, known as chronic high blood pressure, affects approximately 45% of the American population and is a growing condition in other parts of the world, particularly in Asia and Europe. On the other hand, cancer resulted in approximately 10 million deaths in 2020 worldwide. Several studies indicate a coexistence of these two conditions, specifically that hypertension, independently, is associated with an increased risk of cancer. In the present study, we conducted a meta-analysis initially to reveal the prevalence of hypertension and cancer comorbidity and then to assess which organ-specific cancers were associated with hypertension by calculating the summary relative risks (RRs) and 95% confidence intervals (CIs). Our analysis shows that hypertension plays a role in cancer initiation. Our extended analysis on how the hypertension-associated angiogenesis factors are linked to cancer demonstrated that matrix metalloproteinases 2 and 9 appear to be two key factors facilitating cancer in hypertensive patients. This work serves as an important step in the current assessment of hypertension-promoted increased risk of 19 different cancers, particularly kidney, renal cell carcinoma, breast, colorectal, endometrial, and bladder. These findings provide new insight into how to treat and prevent cancer in hypertensive patients.