Does Surgery for Breast Cancer Induce Angiogenesis and Thus Promote Metastasis?

Abstract

At the time of surgery for breast cancer, cancer cells released from the primary tumor have most likely entered blood or lymphatic vessels, leading to the development of micrometastases. Cancer cells directly produce angiogenesis stimulators, provoke the release of stimulators bound to the surrounding extracellular matrix and induce macrophages to secrete angiogenesis stimulators, thereby promoting angiogenesis. Metastasis dormancy is characterized by a balance between cell proliferation and apoptosis and is thought to be controlled by increased apoptosis, indirectly induced by angiogenesis inhibitors. Many patients with solid tumors already have micrometastases at the time of detection and surgical removal of their primary tumors. Primary tumor resection is believed to stimulate angiogenesis, initiating the proliferation of latent micrometastases. Latent micrometastases have already acquired angiogenic potential. The provision of additional therapy to inhibit angiogenesis after surgery is therefore considered a rational approach. The effectiveness of dormancy therapy should be evaluated in the prospective clinical trials of chemotherapy with drugs such as cyclophosphamide and UFT, which have been reported to inhibit angiogenesis as demonstrated by the numbers of circulating endothelial cells and circulating endothelial progenitors in peripheral blood before and after surgery in women with primary breast cancer.

Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?

“…These putative endothelial cell aggregates have hitherto not been reported in patients with renal tumors. It might be speculated that they mirror active angiogenesis in the tumors or during wound healing after surgery [56]. Increased numbers of CECs, probably shed from activated or damaged tumor vessel walls [57,58] and circulating endothelial progenitor cells derived from the bone marrow have been described in the blood of cancer patients and may importantly contribute to cancer growth and metastasis (reviewed in [58-60]).…”

Dormancy in solid tumors: implications for prostate cancer

“…It has been suggested that removal of the primary tumor actually promotes metastasis by stimulating angiogenesis and thus stimulating growth in the micrometastasis [48]. Furthermore, epoxyeicosatrienoic acids (EETs), which stimulate angiogenesis, have been shown to promote release from dormancy in liposarcoma and Lewis lung carcinoma [49].…”

Microenvironmental regulation of therapeutic response in cancer

“…A plethora of proliferative and angiogenic factors, many of which originate in the stromal compartment, are found to be altered in the serum of patients after surgery [209]. Consequently, it has been postulated that the wound’s response contributes to the progression of minimal residual disease and distant, dormant micrometastases after surgery [210–212]. …”