Induction of angiogenesis during the transition from hyperplasia to neoplasia
TL;DR: It is reported here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation, suggesting that induction of angiogenesis is an important step in carcinogenesis.
Abstract: It is now well established that unrestricted growth of tumours is dependent upon angiogenesis. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types is providing a new format for studying multi-step tumorigenesis. In one of these models, transgenic mice expressing an oncogene in the beta-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novel in vitro assay confirms that hyperplasia per se does not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenic in vitro at a time when such islets are neovascularized in vivo and at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.
Citations
More filters
TL;DR: Think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth, which may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
Abstract: Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
7,916 citations
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
6,895 citations
Cites background or methods from "Induction of angiogenesis during th..."
...In human onwas substantiated by histological analysis, which recology, an important application of this capability to vealed two hallmarks of angiogenesis, capillary sproutvisualize capillaries has been the development of new ing and endothelial cell proliferation, in a subset of the prognostic tests for probability of relapse (or diseasehyperplastic islets and in all solid tumors in these free survival) following surgical resection of an invasive transgenic mice (Folkman et al., 1989)....
[...]
...…immunological markers to visualize the vas-thelial cells were cocultured in a three-dimensional colculature has become an important new tool in assessinglagen gel with islets isolated at different ages from the the histopathology of cancerous lesions, as seen forRIP-Tag mice (Folkman et al., 1989)....
[...]
...We defined the angiogenic switch using an in vitro of Two Human Cancers bioassay for angiogenic activity, in which capillary endoThe use of immunological markers to visualize the vasthelial cells were cocultured in a three-dimensional colculature has become an important new tool in assessing lagen gel with islets isolated at different ages from the the histopathology of cancerous lesions, as seen for RIP-Tag mice (Folkman et al., 1989)....
[...]
...…has been the development of newing and endothelial cell proliferation, in a subset of the prognostic tests for probability of relapse (or disease-hyperplastic islets and in all solid tumors in these free survival) following surgical resection of an invasivetransgenic mice (Folkman et al., 1989)....
[...]
TL;DR: The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both).
Abstract: Background. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). Methods. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocyto-chemically for factor VIII. The microvessels were carefully counted (per 200×field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. Results. Both microvessel counts and density grades correlated with metastatic disease. The mean (±SD) count and grade in the patients with metastases were 101±49.3 and 2.95±1.00 vessels, respect...
5,699 citations
TL;DR: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension.
Abstract: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.
4,641 citations
TL;DR: Method of treating a wound or burn which comprises directly dressing its surface with non-woven fabric comprising staple fibers of spun, regenerated collagen substantially free of telopeptides is disclosed.
4,637 citations
References
More filters
TL;DR: This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in 2016 and is likely to be accompanied by neovascularization.
Abstract: THE growth of solid neoplasms is always accompanied by neovascularization. This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in f...
9,874 citations
TL;DR: It is argued the cause-and-effect relationship between in utero exposure to diethylstilbestrol and incidence of vaginal adenocarcinoma among young women and a ban of such diet supplementation of human foodstuffs is called for.
Abstract: Herbst, Ulfelder and Poskanzer1 were the first to notice a high correlation between adenocarcinoma of the vagina in adolescent girls and prior maternal ingestion of diethylstilbestrol. This is a stunning observation. It is supported by five more cases described in this issue by Greenwald et al. In a previous editorial2 Langmuir discussed some clinical and scientific implications of this discovery. Further speculations are now warranted. Neither Herbst nor Greenwald studied a large number of mothers with repeated bleeding or previous pregnancy loss who did not receive stilbestrol. This omission is irrelevant, however, because of the extreme rarity of adenocarcinoma of . . .
2,438 citations
TL;DR: Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin μ or κ enhancer frequently develop a fatal lymphoma within a few months of birth and constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation.
Abstract: Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin mu or kappa enhancer frequently develop a fatal lymphoma within a few months of birth. Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation. These myc mice should aid study of lymphoma development, B-cell ontogeny and immunoglobulin regulation.
1,781 citations
TL;DR: Following the transfer into fertilized mouse eggs of recombinant genes composed of the upstream region of the rat insulin II gene linked to sequences coding for the large-T antigen of simian virus 40, large- T antigen is detected exclusively in the β-Cells of the endocrine pancreas of transgenic mice.
Abstract: Following the transfer into fertilized mouse eggs of recombinant genes composed of the upstream region of the rat insulin II gene linked to sequences coding for the large-T antigen of simian virus 40, large-T antigen is detected exclusively in the beta-cells of the endocrine pancreas of transgenic mice. The alpha- and delta-cells normally found in the islets of Langerhans are rare and disordered. Well-vascularized beta-cell tumours arise in mice harbouring and inheriting these hybrid oncogenes.
1,383 citations
TL;DR: Tumor-induced capillary proliferation was studied in the rabbit cornea after implantation of V2 carcinoma 1 mm from the limbal vascular plexus to suggest that active migration of preformed endothelial cells toward the tumor stimulus may precede cell proliferation during tumor angiogenesis.
1,286 citations