Abstract

Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10–30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.Both primary and metastatic tumors use preexisting host tissue vessels as their blood supply. Tumors may grow to a clinically detectable size without angiogenesis and makes them less likely to respond to drugs designed to target the abnormal vasculature produced by angiogenesis, but further studies to explore the biological and clinical implication of these co-opted vessels is needed.

Highlights

  • Angiogenesis, the development of new blood vessels following the proliferation of the endothelial cells of preexisting vessels, is regarded as a hallmark in cancer development [1]

  • There is, evidence that both primary tumors and metastases are able to progress without angiogenesis

  • Sardari et al [24] used double immunostaining with CD34 and Ki-67 antibodies to assess endothelial cell proliferation fraction and classified Non–small cell lung cancer (NSCLC) into growth patterns (GPs) based on morphological characteristics of the tumor tissue at the invading front; alveolar nonangiogenic, papillary intermediate, and destructive angiogenic

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Summary

Introduction

Angiogenesis, the development of new blood vessels following the proliferation of the endothelial cells of preexisting vessels, is regarded as a hallmark in cancer development [1]. Observations in human brain tissue that demonstrated how a subset of tumors initially grow by co-opting existing host vessels inspired Holash et al to do further studies in murine models [5, 14].

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