Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy

Area of Science:

• Oncology
• Vascular Biology
• Aging Research

Background:

• Human cancers are often diagnosed and treated in older individuals with prevalent vascular diseases.
• Current cancer research models typically use young, healthy mice, not reflecting the aged human population.
• Age-related vascular conditions like atherosclerosis are rarely considered in the context of cancer therapy outcomes.

Purpose of the Study:

• To investigate the impact of natural aging and atherosclerosis on tumor growth, angiogenesis, and response to antiangiogenic therapy.
• To compare tumor progression and therapeutic responses in young, healthy mice versus old and atherosclerotic mice.

Main Methods:

• Transplantation of Lewis lung carcinoma and B16F1 tumors into young (4-8 weeks) and old (12-18 months) ApoE(+/+) and ApoE(-/-) mice.
• Assessment of tumor growth rates, vascularity, tumor endothelial marker 1 (TEM-1) expression, and tumor hypoxia.
• Analysis of circulating CD45(-)/VEGFR(+) cells and ex vivo endothelial sprouting.
• Evaluation of metronomic cyclophosphamide therapy efficacy in different mouse models.

Main Results:

• Tumors grew faster in young, non-atherosclerotic mice compared to old or atherosclerotic (old/ApoE(-/-)) mice.
• Age-related changes included reduced tumor vascularity, lower TEM-1 expression, increased hypoxia, and depleted circulating VEGFR(+) cells.
• Endothelial sprouting ex vivo was impaired in older/atherosclerotic models.
• Metronomic cyclophosphamide therapy showed reduced efficacy in atherosclerotic mice.

Conclusions:

• Vascular aging and atherosclerosis significantly alter tumor progression and angiogenesis.
• These vascular conditions may impair the effectiveness of antiangiogenic therapies in cancer treatment.
• The study highlights the need to consider patient vascular health in cancer therapy strategies.