Heart disease is a serious condition, and cancer is an even-more-worrisome disease. Now, a unique Israeli has found that there is a connection between heart disease and cancer. The findings, published in the prestigious journal Circulation under the title “Early Cardiac Remodeling Promotes Tumor Growth and Metastasis,” published in Circulation, could potentially help cardio-oncologists slow cancer progression and improve patients’ conditions.
Prof. Ami Aronheim, Prof. Yuval Shaked, and Dr. Shimrit Avraham of Rapoport Faculty of Medicine at the Technion-Israel Institute of Technology in Haifa, together with Prof. Walid Saliba and Prof. Avinoam Shiran from nearby Carmel Medical Center found that early changes in the heart resulting from cardiac damage (referred to as cardiac remodeling, a group of molecular, cellular and fibrous changes that show up in size, mass, geometry and function of the heart after injury) promotes cancer progression.
There have been indications that cancer and cardiovascular diseases are linked and that heart failure and stress can result in a poor cancer prognosis. While chemotherapy drugs could damage heart muscle, the effects of cardiac remodeling on cancer have not been well known. To uncover the connection between cardiac remodeling and cancer, the Haifa team investigated whether early cardiac remodeling in the absence of heart failure promotes cancer.
To mimic cardiac remodeling, the research team collaborated with the Preclinical Research Authority led by Dr. Rona Shofti and Dr. Tali Haas and used a laboratory technique called transverse aortic constriction (TAC) to exert mechanical pressure on the hearts of lab mice. TAC causes stress to the mouse resulting in an increase in heart cell growth called hypertrophy, which is a common effect of cardiovascular complications. The team then implanted cancer cells into the TAC-operated mice to see if the early cardiac remodeling affects tumor progression.
The researchers found that the TAC-operated mice developed larger tumors at the site of the implanted cancer cells. In addition, TAC-operated mice displayed a higher rate of cancer cells spreading to the lungs, representing metastases (secondary tumors spread from the original tumor) as compared to mice that had not undergone the surgery.
The investigators also found that serum from TAC-operated mice resulted in enhanced cancer cell proliferation in cell cultures in vitro (outside a whole organism, suggesting that tumor-promoting proteins are present in the blood from the TAC-operated mice. Specifically, a protein called Periostin, which is highly expressed in the hearts of the TAC-operated mice. To investigate the effects of Periostin, on cancer cells, the researchers studied how it affected cancer cells in vitro. They found that the addition of purified Periostin enhanced cancer cell proliferation, and that the depletion of Periostin from mouse serum lowered cancer cell proliferation (in vitro).
The results of the study highlight the connection between cardiovascular disease and cancer and the importance of early diagnosis and treatment of cardiac disease in cancer patients. Such intervention can to significantly slow the advance of cancer and improve the patient’s condition.
“As a result of the study, we recommend that you treat heart problems early, when the body is still successfully coping with the problem, and not wait for a chronic condition,” concluded Aronheim. “Such problems can be detected with a simple echocardiography test, and in many cases, early catheterization may help to slow cancerous development.”
