Chronologic aging decreases tumor angiogenesis and metastasis in a mouse model of head and neck cancer

Abstract

Abstract. The incidence of malignant tumors increases with age. This may be due to the duration of carcinogenesis or age related changes providing a favorable environment for tumor formation. Aging is associated with molecular, cellular and physiological events that influence carcinogenesis and cancer growth. Physiologic cell proliferation, differentiation, and aging can result in cell death. However, under the influence of exogenous or endogenous factors cells can undergo pathologic dedifferentiation, immortalization, and neoplastic clone formation. The effects of age have been recognized in both animal and human malignancies. These processes can result in cellular senescence as a barrier to tumorigenesis. Inducing senescence is an important outcome for the successful treatment of cancers particularly those resistant to apoptosis. Senescence is associated with polyploidy in several human cell lines. Polyploid cells are dangerous in that they can undergo aberrant mitoses giving rise to unstable progeny. Polyploid cells have been shown to escape senescence and divide. We examined the effects of aging on squamous cell carcinoma formation in a mouse model. Chronologically aged mice experience shorter tumor latency periods than wildtype animals. Tumors in aged mice were poorly vascularized, necrotic, and produced significantly fewer cervical lymph node metastases. Vascular endothelial growth factor expression was similar in primary tumors from young and old mice, but microvessel density was significantly reduced in tumors arising in aged mice. These results indicate that host response to angiogenic factors inhibit tumor growth and metastasis of head and neck cancer.

Nanomedicine in Oncocardiology: Contribution and Perspectives of Preclinical Studies

“…The physiological differences between young and old animals are significant, and one example is related to the EPR effect. Tumor-bearing young animals may exhibit a more pronounced EPR effect than older animals since older subjects present a lower tumor angiogenesis rate ( 31 ). This issue makes less probable the formation of blood vessels with fenestrations allowing the higher permeation of nanocarriers by tumor tissues in young animals compared to older subjects ( 32 ).…”