Abstract Body: Introduction
It has been demonstrated that CVD promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, e.g. inflammation and oxidative stress, that could explain why patients with CVD are prone to develop cancer.
Recent reports also suggest a link between hypertension, hypertrophy and lung cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth.
Hypothesis
We hypothesized that ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth.
Methods
ANGII (2000 ng.kg^-1.min^-1; 4w) was administered to 10w old C57B6/J mice using osmotic minipumps. After 4w, pumps were removed and 5*10⁵ Lewis lung carcinoma (LLC) cells injected onto the right flank. To study the direct impact of the ANGII peptide on the cancer growth mice were treated with ANGII as mentioned above and LLC cells were injected after 3w to allow concomitant ANGII treatment and cancer growth. A similar experiment was performed by injecting 2*10⁵ MC38 colon cancer cells. Tumor growth was monitored for 21d after which the mice were sacrificed. Results are expressed as mean ± SEM.
Results
ANGII treatment concomitantly with cancer growth resulted in significantly larger tumors as shown by post-mortem tumor volume (881 ± 111 control vs. 1467 ± 154 mm^3 ANGII, P=0.013). In contrast, no increased tumor growth was observed when ANGII was administered non-concomitant with cancer growth. Interestingly, MC38 tumor growth significantly decreased in the ANGII treated group as portrayed by tumor volume (462 ± 65 control vs. 227 ± 81 mm^3 ANGII).
Conclusion
Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.