Re: Initial Stages of Tumor Cell-Induced Angiogenesis: Evaluation Via Skin Window Chambers in Rodent Models
Year: 2000
Type: letter
Abstract: The recent report by Li et al. in the Journal (1) has provided new insights in the relationship of tumor cells and host vasculature at very early stages of tumor formation. Four stages of early angiogenesis were visualized: 1) migration of tumor cells toward existing vasculature, 2) vasodilation and increased tortuosity of host vessels at the 60- to 80-cell stage of tumor growth, 3) tumor vessel formation at the 100- to 300-cell stage of tumor formation, and 4) co-invasion of developing neovasculature with the growing tumor into surrounding normal tissue. Li et al. (1) also showed that angiogenesis inhibitors can prevent tumor growth at these early stages of tumor formation. These observations differ from previous results that suggested the angiogenesis process started later in tumor development. These important observations by Li et al. (1) were made possible by the use of green fluorescent protein (GFP)-expressing tumor cells that were inoculated into skin window chambers in rats and mice. Readers of the article by Li et al. (1) should find it interesting and important to know that the use of GFP-expressing tumor cells may enable additional critical observations with regard to tumor cell growth, metastasis, and angiogenesis. In the original publications on the development of stably expressing GFP tumor cells, we demonstrated that single cells and small colonies could be visualized in numerous live organs after spontaneous metastasis (2,3). As Li et al. (1) point out, angiogenesis initiation in metastatic tumors may be very different from that of primary tumors. Since Li et al. suggest a paradigm change in our concepts of early angiogenesis of tumors based on observations in a skin window model, it is critical to investigate this stage of angiogenesis in spontaneous metastasis resembling that which occurs in clinical cancer. Examples using GFP-expressing tumor cells that enable such investigations include orthotopic metastatic models of prostate, lung, and other cancer types (3–5). In addition, stable, very high expression GFP tumor cells developed by multiple-step selection with drug-resistant markers linked to GFP vectors and further selected for brightness in the absence of drugs in vitro have proven to be very bright, stable, and useful for visualizing and tracking tumor cells and angiogenesis in vivo (2–5). Such GFP tumor cells are so bright that they can enable noninvasive whole-body imaging of tumors, metastases, and angiogenesis in real-time [(6,7); Yang M, Baranov E, Hoffman RM: unpublished observations].
Author: R. M. Hoffman
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4245866457