Evaluation of renal cancer progression in a mouse model of heart failure

Shi, Canxia; Aboumsallem, Joseph Pierre; Wit, Sanne de; Schouten, Elisabeth Maria; Bračun, Valentina; Meijers, Wouter C.; Silljé, Herman H W; Boer, Rudolf A. de

doi:10.1002/cac2.12185

Cited by 11 publications

(17 citation statements)

References 12 publications

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“…It is hypothesized that the indirect effects are mediated as well by secreted factors, which impose the monocytes “education” in the bone marrow. Previous studies suggested that HF effects on cancer cells are not generic, and it is dependent on the type of cancer ( 31 ). Whether or not HF and tumor cross-talk is dependent on the pathophysiologic basis leading to heart HF is questionable.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Aronheim¹

2022

Cancer Research

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Heart failure and cancer are the leading cause of deaths worldwide. While heart failure and cancer have been considered separate diseases, it is becoming evident that they are highly connected and affect each other's outcomes. Recent studies using experimental mouse models have suggested that heart failure promotes tumor progression. The mouse models used involve major irreversible surgery. Here, we induced heart hypertrophy via expression of Activating Transcription Factor 3 (ATF3) in cardiomyocytes followed by cancer cells implantation. Tumors developing in ATF3-transgenic mice grew larger and displayed a more highly metastatic phenotype compared to tumors in wild-type mice. To address whether ATF3 expression or the cardiac outcome are necessary for tumor progression, ATF3 expression was turned off after cardiac hypertrophy development followed by cancer cell implantation. The tumor promotion phenotype as well as the enhancement of metastatic properties were preserved, suggesting that the failing heart per se is sufficient to promote tumor progression. Serum derived from ATF3-transgenic mice enhanced cancer cell proliferation and increased cancer cell metastatic properties in vitro. Using a cytokine array panel, multiple factors responsible for promoting tumor cell proliferation and the metastatic phenotype were identified. Interestingly, the failing heart and the tumor separately and simultaneously contributed to higher levels of these factors in the serum as well as other tissues and organs. These data suggest the existence of intimate crosstalk between the hypertrophied heart and the tumor which is mediated by secreted factors leading to cancer promotion and disease deterioration.

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Section: Discussionmentioning

confidence: 99%

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Aronheim¹

2022

Cancer Research

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“…However, despite multiple layers of evidence that HF can stimulate tumour growth, these effects were not reproduced in a mouse model of renal cancer, suggesting that the tumour promoting effects of HF might be cancer-site specific. 17 …”

Section: Bidirectional Interaction Between Hf and Cancermentioning

confidence: 99%

Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Wit

Glen

Boer

et al. 2022

Cardiovascular Research

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Heart failure (HF) and cancer are the leading causes of death worldwide and accumulating evidence demonstrates that HF and cancer affect one another in a bidirectional way. Patients with HF are at increased risk for developing cancer, and HF is associated with accelerated tumour growth. The presence of malignancy may induce systemic metabolic, inflammatory, and microbial alterations resulting in impaired cardiac function. In addition to pathophysiologic mechanisms that are shared between cancer and HF, overlaps also exist between pathways required for normal cardiac physiology and for tumour growth. Therefore, these overlaps may also explain the increased risk for cardiotoxicity and HF as a result of targeted anti-cancer therapies. This review provides an overview of mechanisms involved in the bidirectional connection between HF and cancer, specifically focusing upon current ‘hot-topics’ in these shared mechanisms. It subsequently describes targeted anti-cancer therapies with cardiotoxic potential as a result of overlap between their anti-cancer targets and pathways required for normal cardiac function.

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“…However, contradictory findings have also been reported. HF did not increase tumor growth in a mouse model for kidney cancer, 5 suggesting the effects of HF on tumor growth appear to be cancer type or site specific. Furthermore, most models studied HF with left ventricular (LV) dysfunction.…”

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confidence: 98%

“…[2][3][4] Our current study builds on the growing evidence that HF and cardiac hypertrophy can promote cancer growth. However, not all tumor models were affected by HF, 5 suggesting not all cancer types are susceptible to HFinduced tumor growth. It is important to further explore which cancer types are affected by HF and which HF phenotypes can stimulate tumor progression.…”

mentioning

confidence: 99%

“…The Masson trichrome staining was performed, and LV RNA levels were measured using quantitative polymerase chain reaction, as described previously. 5 TAC surgery resulted in an increase in heart weight (P<0.0001), LV wall thickness (P<0.0001), and LV fibrosis (P=0.0019), as well as increased expression of ANP (atrial natriuretic peptide; P=0.0011) and fibrotic markers TIMP1 (tissue inhibitor of metalloprotease-1; P<0.0001) and COL1A1 (collagen type I alpha 1 chain; P=0.0007; Figure [A through C, F, G]). However, LV ejection fraction (P=0.6590) and global longitudinal strain (P=0.5360) were preserved in TAC mice (Figure [D and E]).…”

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confidence: 99%

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Pressure Overload–Induced Cardiac Hypertrophy Stimulates Tumor Growth in Tumor-Prone Apc ^Min Mice

de Wit,

Aboumsallem,

Shi

et al. 2023

Circ: Heart Failure

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Evaluation of renal cancer progression in a mouse model of heart failure

Cited by 11 publications

References 12 publications

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Pressure Overload–Induced Cardiac Hypertrophy Stimulates Tumor Growth in Tumor-Prone Apc ^Min Mice

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Evaluation of renal cancer progression in a mouse model of heart failure

Cited by 11 publications

References 12 publications

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Pressure Overload–Induced Cardiac Hypertrophy Stimulates Tumor Growth in Tumor-Prone Apc Min Mice

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Pressure Overload–Induced Cardiac Hypertrophy Stimulates Tumor Growth in Tumor-Prone Apc ^Min Mice