Angiogenesis: A Marker for Neoplastic Transformation of Mammary Papillary Hyperplasia

Brem, Steven; Gullino, Pietro M.; Medina, Daniel

doi:10.1126/science.402692

Cited by 151 publications

(57 citation statements)

References 17 publications

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“…Furthermore, tissues of higher predicted tumour incidence induced greater neo-vascular responses than did those with a lower probability of malignant transformation. These findings have been confirmed in a number of similar studies (Guinebretiere et al, 1994;Brem et al, 1977;Lichtenbeld et al, 1998). We therefore felt that it was reasonable to hypothesize that changes in periductal vascularity may precede the development of invasive carcinoma in DCIS.…”

Section: Discussionsupporting

confidence: 63%

“…In DCIS and other precursor lesions (Guidi et al, 1994;Engels et al, 1997a,b;Lee et al, 1997;Lee et al, 1999;Sales et al, 1999;Valtola et al, 1999), two patterns of vascularity have been described: diffuse stromal vascularity and a vascular rim around the involved ducts. Pre-malignant lesions of the breast can induce angiogenesis in animal experimental systems and in the human breast (Gimbrone and Gullino, 1976;Brem et al, 1977;Heffelfinger et al, 1996;Lichtenbeld et al, 1998), it thus seems possible that the pattern or extent of vascularisation around DCIS may be an important factor in determining the transformation from in situ to invasive carcinoma. It is likely that the periductal vessels are most important in this respect as incipient invasion is most likely to be associated with changes in vessels in the immediate vicinity of the tumour cells.…”

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confidence: 99%

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Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

et al. 2002

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Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34 + and CD31 + vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34 + and CD141 + vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34 + and CD141 + vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions.

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Section: Discussionsupporting

confidence: 63%

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confidence: 99%

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

et al. 2002

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“…One of the better characterised among such angiogenic factors is basic Fibroblast Growth Factor (bFGF) (Rifkin & Moscatelli, 1989), whose presence in a large number of normal and malignant cells is well established, and that has been implicated as a major contributing factor in both physiological and pathological neovessel formation (Folkman et al, 1988;Klagsbrun et al, 1986;Thompson et al, 1988;Hayek et al, 1987). Since solid tumour growth and progression are strictly dependent from neovessel formation (Folkman et al, 1989;Brem et al, 1977) interfering with this process by counteracting the effect of angiogenic growth factors could represent a novel and selective therapeutic approach to malignancy.Suramin, a polysulphonated trypan red derivative used in the past as antitrypanosomic agent (Hawking et al, 1987), has recently generated interest as an antinoplastic agent (Stein et al, 1989;Myers et al, 1990; Richard, 1990;Hosang, 1985;Mills et al, 1990) to their cell surface receptors through direct complexation of the growth factors and/or via a modification of the cell receptor (Coffey et al, 1987). This activity could explain suramin inhibition of the in vitro growth of a number of cell lines (Spiegelman et al, 1987;Pienta et al, 1991; Kim et al, 1991 …”

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confidence: 99%

Suramin prevents neovascularisation and tumour growth through blocking of basic fibroblast growth factor activity

Pesenti¹,

Sola²,

Mongelli³

et al. 1992

Br J Cancer

110

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Summary Inhibition of angiogenesis through blocking of growth factors involved in this process could be a novel therapeutic approach in several important pathologies, neoplasia among them. Suramin has recently been described to possess antineoplastic activity in animals and humans, and it has been proposed that an important role in this activity is played by antagonism of growth factors and especially bFGF. To investigate this hypothesis in vivo, we used gelatin sponges loaded with bFGF and implanted subcutaneously in mice. Suramin showed an inhibitory activity on bFGF-induced angiogenesis, whereas it was inactive in the case of heparin-complexed bFGF. Suramin was also studied in an in vivo model of tumour-induced angiogenesis using the murine M5076 reticulosarcoma, a tumour producing significant levels of bFGF. Suramin was able to reduce tumour growth and tumour induced angiogenesis, and exogenous administration of bFGF countered suramin effects.Physiologically, angiogenesis (i.e. the formation of new capillary vessels), is an important event in embryonic development and in the adult female reproductive cycle (Gospodarowicz & Thakral, 1978). Under pathological conditions neovascularisation occurs during the wound healing process (Knighton, 1981) and in a variety of diseases ranging from diabetic retinopathy to psoriasis and several types of chronic inflammations (Goldie, 1969). It has also been shown that the process of solid tumours growth is angiogenesisdependent (Gullino, 1978;Folkman, 1990). Several substances of different chemical nature and cellular origin, including growth factors produced by the neoplastic cells themselves, have been described to be involved in tumourinduced neoangiogenesis (Shing et al., 1985;Folkman & Klagsbrun, 1987) by directly and/or indirectly stimulating endothelial cells proliferation and/or migration (Ausprunk & Folkman, 1977). One of the better characterised among such angiogenic factors is basic Fibroblast Growth Factor (bFGF) (Rifkin & Moscatelli, 1989), whose presence in a large number of normal and malignant cells is well established, and that has been implicated as a major contributing factor in both physiological and pathological neovessel formation (Folkman et al., 1988;Klagsbrun et al., 1986;Thompson et al., 1988;Hayek et al., 1987). Since solid tumour growth and progression are strictly dependent from neovessel formation (Folkman et al., 1989;Brem et al., 1977) interfering with this process by counteracting the effect of angiogenic growth factors could represent a novel and selective therapeutic approach to malignancy.Suramin, a polysulphonated trypan red derivative used in the past as antitrypanosomic agent (Hawking et al., 1987), has recently generated interest as an antinoplastic agent (Stein et al., 1989;Myers et al., 1990; Richard, 1990;Hosang, 1985;Mills et al., 1990) to their cell surface receptors through direct complexation of the growth factors and/or via a modification of the cell receptor (Coffey et al., 1987). This activity could explain suramin inhibitio...

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“…Again, in the mouse angiogenesis, a property of carcinomas but not of resting mammary gland, appears earlier than any morphological evidence of malignancy in mouse papillomas which frequently progress toward invasive carcinoma (Brem et al, 1977).…”

Section: Discussionmentioning

confidence: 83%

A study of false positive and negative responses in the tube leucocyte adherence inhibition (tube LAI) assay

O’Connor¹,

MacFarlane²,

Murray³

et al. 1978

Br J Cancer

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Summary.-A panel of 5 different breast-cancer and 2 other cancer extracts was used to clarify the false-negative responses in patients with Stage I and II breast cancer and the false-positive responses in control subjects. Most patients with Stage I and II breast cancer who had an initially negative LAI response were positive when tested against the panel. The false negatives occurred because of (1) the experimental errors of the assay; (2) changes in the antigenic strength of the extracts; (3) antigenic heterogeneity of a few tumours and (4) lack of tumour-specific reactivity of the host. 3%0 of control subjects had a false-positive LAI response. The leucocytes from most of these positive patients did not react to the panel of antigens, and hence the false positives appeared to result from experimental error. In-hospital patients with benign breast disease had a 12% positivity rate when initially assayed, and 63% of these patients reacted to the panel of breast-cancer antigens. Those patients with benign breast disease who reacted to the panel of breast-cancer antigens had cytophilic anti -breast -cancer antibody in their serum; their leucocyte LAI reactivity was blocked in an immunologically specific manner by serum from advanced Stage IV breast-cancer patients; their leucocytes reacted to extracts of breast cancer and not fibrocystic breast tissue; their leucocyte reactivity was blocked by isolated breastcancer TSA that was linked to /2 microglobulin, but not by normal breast-tissue proteins; and the kinetics of the LAI response after excision of the breast mass was identical to that observed with breast-cancer patients after mastectomy. In these patients, the breast tissue within the breast lump expressed breast TSA similar to unequivocal breast cancer.

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Angiogenesis: A Marker for Neoplastic Transformation of Mammary Papillary Hyperplasia

Cited by 151 publications

References 17 publications

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

Suramin prevents neovascularisation and tumour growth through blocking of basic fibroblast growth factor activity

A study of false positive and negative responses in the tube leucocyte adherence inhibition (tube LAI) assay

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