Cardiac Dysfunction Promotes Cancer Progression via Multiple Secreted Factors

Area of Science:

• Cardiology
• Oncology
• Molecular Biology

Background:

• Heart failure and cancer are leading global causes of death.
• Emerging evidence suggests a significant interplay between heart failure and cancer progression.
• Previous models for studying this interaction involved invasive surgical procedures.

Purpose of the Study:

• To investigate the causal link between cardiac hypertrophy and tumor progression.
• To determine if the failing heart itself, independent of specific molecular triggers, promotes cancer.
• To identify the mechanisms underlying the cross-talk between cardiac dysfunction and cancer.

Main Methods:

• Induced cardiac hypertrophy in mice by expressing activating transcription factor 3 (ATF3) in cardiomyocytes.
• Implanted cancer cells into mice with induced cardiac hypertrophy.
• Reversibly inhibited ATF3 expression to differentiate between gene effects and cardiac outcome effects.
• Analyzed tumor growth, metastasis, and serum factors using cytokine arrays.

Main Results:

• Tumors in mice with cardiac hypertrophy exhibited larger size and increased metastatic potential.
• The tumor-promoting and metastatic phenotype persisted even after ATF3 expression was turned off, indicating the failing heart's sufficiency.
• Serum from affected mice enhanced cancer cell proliferation and metastasis in vitro.
• Identified specific secreted factors mediating the cross-talk between the failing heart and tumors.

Conclusions:

• Cardiac hypertrophy and heart failure are sufficient to promote cancer progression and metastasis.
• A complex cross-talk exists between the hypertrophied heart and tumors, mediated by secreted factors.
• Early diagnosis and treatment of heart failure are crucial to prevent exacerbation of cancer progression.