Blocking basement membrane collagen deposition inhibits the growth of 7,12-dimethylbenzanthracene-induced rat mammary tumors

Wicha, Max S.; Liotta, Lance A.; Lewko, Walter M.; Kidwell, William R.

doi:10.1016/0304-3835(81)90032-x

Cited by 14 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that primary cultures ofrat mammary epithelium, consisting ofductal and alveolar organoids, attach to tissue culture dishes over 10-18 hr and rapidly spread and flatten (19). Autoradiography reveals that these cultures undergo several rounds of DNA synthesis in the first week.…”

Section: Resultsmentioning

confidence: 99%

“…Due to the high lipid content of the mammary tissue it was necessary to repeat the delipidation procedure at least two times until the lipid was removed as determined by oil-O-red staining (19 described (9). Twenty-four hours after cells were plated on these gels they were released to float as described by Emerman and Pitelka (10,11).…”

mentioning

confidence: 99%

“…Twenty-four hours after cells were plated on these gels they were released to float as described by Emerman and Pitelka (10,11). Autoradiography and [3H]thymidine incorporation into DNA were performed as we have described (19). DNA measurements were done by fluorometric assay as described by Setaro and Morley (20).…”

mentioning

confidence: 99%

“…Rat a-lactalbumin and rabbit antibody to rat a-lactalbumin were a generous gift of the National Institutes of Health Breast Cancer Task Force. Indirect immunofluorescence localization of a-lactalbumin was performed on air-dried cultures as we have described (19). Radioimmunoassay for a-lactalbumin was carried out with a-lactalbumin iodinated by the lactoperoxidase method as described by Quasba and Gullino (21) (see Fig.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Extracellular matrix promotes mammary epithelial growth and differentiation in vitro.

Wicha¹,

Lowrie²,

Kohn³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

226

101

View full text Add to dashboard Cite

The study of growth and differentiation of mammary epithelium has been hampered by the difficulty of maintaining these functions in vitro. We describe a system for the primary culture of rat mammary epithelium on an acellular matrix derived from whole rat mammary glands that maintains growth and differentiation for months. Cultures plated on this complex substratum produce 50 times the ei-lactalbumin of those on tissue culture dishes and 5 times the a-lactalbumin of those on floating collagen gels as determined by radioimmunoassay. Unlike cultures grown on floating collagen gels, which rapidly lose the ability to secrete the milk sugar lactose, mammary cells on this matrix retain this ability for over 30 days in culture. The organ specificity ofthis mammary extracellular material is shown by the failure of extracellular matrix prepared from rat liver to support mammary differentiation. Within a given culture dish, cells on the surface of mammary extracellular matrix are more differentiated than those on the adjacent plastic. This is demonstrated by their increased a-lactalbumin content as shown by indirect immunofluorescence, and by their increased ability to bind fluorescein-conjugated peanut lectin. Cells on the surface ofthe matrix continue to synthesize DNA as determined by [3H]thymidine incorporation and autoradiography. Even when mammary epithelial cells are plated at low density, cell division continues until the matrix is covered with a confluent layer. We propose that the limited growth, differentiation, and survival of mammary cells in previously described in vitro systems may have been due to substrata that were inadequate to support these functions.The study of mammary growth and differentiation has been hampered by the lack of a suitable system that is capable of maintaining these functions in vitro. When normal mammary epithelial cells from rodents or humans are cultured on tissue culture plastic surfaces they undergo only a few rounds of cell division and rapidly lose differentiated function (1-3). Sometimes, continuous cell lines that are easy to manipulate in vitro can be established from these cultures (4, 5). However, because these cells are highly selected to proliferate under artificial conditions, their control mechanisms may have little relevance to those ofmammary cells in vivo. Organ culture has the advantage of maintaining more normal tissue orientations. However, these systems have limited viability and the presence of stromal cells makes quantitation of epithelial growth difficult (6, 7).It has been appreciated for some time that cell behavior in vitro may be influenced by placing cells on matrices of stromal collagen (8,9). More recently, Emerman and Pitelka described a system for the culture ofmouse mammary cells on floating gels of stromal collagen. Mammary epithelial cells isolated from midpregnant mice produced considerably more ofthe milk protein casein when plated on these floating collagen gels than when plated on attached collagen gels or tissue culture plastic dishe...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Extracellular matrix promotes mammary epithelial growth and differentiation in vitro.

Wicha¹,

Lowrie²,

Kohn³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

226

101

View full text Add to dashboard Cite

show abstract

“…Formation of collagen is characteristic of differentiated tumors such as those induced by DMBA (Bano et al, 1983). cisHydroxyproline blocks collagen synthesis 10 times more efficiently than total protein synthesis in cultured mammary epithelium and blocks the growth of DMBA-and MNU-induced mammary tumors in vivo Wicha et al, 1981). This clearly indicates that collagen is essential for the growth of mammary tumors.…”

Section: Introductionmentioning

confidence: 94%

Influence of estradiol on mammary tumor collagen solubility in DMBA‐induced rat mammary tumors

Lakshmanaswamy

Balasubramanian

Arunakaran

et al. 2006

Cell Biology International

View full text Add to dashboard Cite

Estradiol plays a vital role in the growth and development of mammary glands. It is a potent stimulator of metabolic processes in normal and carcinoma breast. A critical factor in determining mammary glandular morphology is the stroma. Collagen is a predominant component of the extracellular matrix and cell-collagen interactions are essential carcinogenesis. The present investigation explored the influence of estradiol on collagen solubility and metabolism in mammary tumors during tumor progression and regression. A single injection of 20 mg of 9,10-dimethyl-1,2-benzanthracene was given to rats at 7 weeks of age. With the appearance of the first palpable mammary tumor, the rats were treated with 0.5 microg estradiol or 50 microg tamoxifen daily for 30 days. The rats were sacrificed 24 h after 30 days of treatment. Estradiol appears to stimulate the synthesis of new collagens and thus contributes to the enlargement of the mammary tumors. This might have created a potential microenvironment by increasing the synthesis of suitable matrix that sustains the growth of the mammary tumors. In short, the present findings emphasize a definite mediatory role for collagen in estradiol promoted mammary tumor growth.

show abstract

Effects of cis‐4‐hydroxy‐L‐proline on the androgen‐lnduced growth of the prostate of the prepubertally castrated guinea pig

Wong

Chan

1993

The Prostate

View full text Add to dashboard Cite

The present study examined the effects of cis-4-hydroxy-L-proline (CHP), a proline analog, on the androgen-induced growth of the lateral prostate of prepubertally castrated guinea pigs. Prepubertal male guinea pigs were castrated at the age of 3 weeks and allowed to recover completely before subjection to an experimental regime to alter the stromal collagen synthesis by CHP. The animals were kept on a special proline-deficient diet (PDD) for a week before the subcutaneous injection of CHP (200 mg/kg/day) for 3 days, followed by a combined injection of CHP and dihydrotestosterone (DHT) (10 mg/kg/day) for 10 days. Control animals were injected with saline and DHT only. At the end of the experiment, the lateral prostate was removed and examined by 1) conventional transmission electron microscopy (TEM), 2) staining of proteoglycans (PGs) by Cuprolinic Blue (CB) using the critical electrolyte concentration (CEC) method, 3) carbohydrate and lectin histochemistry, and 4) electron microscopy (EM) lectin-gold labelling. The results showed that the wet weight of prostate from CHP-treated animals was significantly lower than the control and recovery groups. The epithelium was low columnar with an obvious increase in intercellular spaces and number of basal cells. The glandular cells showed little secretory activity with a decrease in number of granular endoplasmic reticulum (GER) profiles, secretory granules, and a small Golgi apparatus. The stroma was composed of stromal cells separated by large intercellular spaces with very sparse collagen fibrils, and a decrease in stromal PGs especially those PGs normally associated with collagen fibrils. CHP treatment also caused perturbation and disorganization in the epithelial basement membrane. The results suggested that stromal collagen is essential in mediating the response of glandular cells to DHT stimulation. Defective stromal collagens hamper the responsiveness of prostatic gland to androgen.

show abstract

Blocking basement membrane collagen deposition inhibits the growth of 7,12-dimethylbenzanthracene-induced rat mammary tumors

Cited by 14 publications

References 12 publications

Extracellular matrix promotes mammary epithelial growth and differentiation in vitro.

Extracellular matrix promotes mammary epithelial growth and differentiation in vitro.

Influence of estradiol on mammary tumor collagen solubility in DMBA‐induced rat mammary tumors

Effects of cis‐4‐hydroxy‐L‐proline on the androgen‐lnduced growth of the prostate of the prepubertally castrated guinea pig

Contact Info

Product

Resources

About