Inappropriate production of collagen and prolyl hydroxylase by human breast cancer cells in vivo

Al-Adnani, M. S.; Kirrane, James; McGee, J O

doi:10.1038/bjc.1975.112

Cited by 43 publications

(18 citation statements)

References 17 publications

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“…There has been considerable controversy as to whether the tumour cells themselves (Al-Adanani et al, 1975;Niitsu et al, 1988), or the fibroblasts in the vicinity of the tumour cells, are stimulated to produce type I collagen (Barsky et al, 1982;Ohtani et al, 1992;Hewitt et al, 1993). Early studies claimed that the excess production of type I collagen is not due to increased collagen synthesis by the stromal fibroblasts, but that it is produced by the breast cancer cells themselves, which suggested that this response was an inappropriate rather than a deliberate host response (Al-Adanani et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…Early studies claimed that the excess production of type I collagen is not due to increased collagen synthesis by the stromal fibroblasts, but that it is produced by the breast cancer cells themselves, which suggested that this response was an inappropriate rather than a deliberate host response (Al-Adanani et al, 1975). Subsequent studies have shown that stromal fibroblasts do, in fact, produce the excess collagen and that the epithelial cells are not responsible for the desmoplastic effect (Barsky et al, 1982;Ohtani et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts

et al. 1999

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This study investigated the modulation of type I collagen gene expression in normal fibroblasts by breast tumour cells. Northern analysis of total RNA extracted from stages I, II and III breast tumour tissue revealed that collagen mRNA levels were elevated in stage I tumours compared to the adjacent normal breast tissues, whereas they were decreased in stages II and III breast tumours. This aberrant collagen gene expression was confirmed by non-radioactive RNA:RNA in situ hybridization analysis of 30 breast carcinomas which localized the production of type I collagen mRNA to the stromal fibroblasts within the vicinity of the tumour cells. In order to determine whether the tumour cells were directly responsible for this altered collagen production by the adjacent fibroblasts, breast tumour cell lines were co-cultured with normal fibroblasts for in vitro assessment of collagen and steady-state collagen RNA levels. Co-culture of tumour cells and normal fibroblasts in the same dish resulted in down-regulation of collagen mRNA and protein. Treatment of the fibroblasts with tumour-cell conditioned medium also resulted in decreased collagen protein levels but the mRNA levels, however, remained unaltered. These results suggested that the tumour cells either secrete a labile ‘factor’, or express a cell surface protein requiring direct contact with the fibroblasts, resulting in down-regulation of collagen gene expression. Modulation of the ECM is a common characteristic of invading tumour cells and usually involves increased production of collagenases by the tumour cells or stromal fibroblasts. This study showed that tumour cells were also able to modulate collagen mRNA production by stromal fibroblasts, which may facilitate tumour cell invasion and metastasis. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts

et al. 1999

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“…However, such cell types were not observed except very occasionally in the region of the tumor. Therefore, from our results, we find it hard to believe that the occa sional fibroblasts which are found scattered in the It has been suggested that the stroma of cancers at various sites such as the breast, esophagus, and stomach are the product of the tumor cells [Shivas and Macken zie, 1974;Al-Adnani et al, 1975;Battifora, 1976;Sakakibara et al, 1982;Al-Zuhair et al, 1986]. The present study is yet another confirmation of the involvement of the cancer cells in the production of the various stromal elements.…”

Section: Discussionmentioning

confidence: 75%

“…Several workers have pointed out that 'infiltrating' carcinoma cells of the breast secrete their own collagen, elastic tissue, and possibly other intermediate fibrillar elements of the stroma inappropriately [Douglas and Shivas, 1974;Shivas and Mackenzie, 1974;Al-Adnani et al, 1975;Albrechtsen et al, 1981;Al-Zuhair et al, 1986], The stroma of cancers at other sites, such as the esophagus and stomach, were occasionally studied [Battifora, 1976;Sakakibara et al, 1982].…”

Section: Methodsmentioning

confidence: 99%

Patterns of Stromal Elements in an Implanted Ureteric Transitional Cell Carcinoma

Al-Zuhair¹,

Al-Adnani²,

Al-Bader³

et al. 1987

Eur Urol

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“…In scirrhous carcinoma, there have been divergent opinions for some time whether the mechanism of collagen increase in the tumour is due to primary production by the tumour cells (Sakakibara et al, 1982;Takeuchi, 1976;Roesel et al, 1978;Al-Adnani et al, 1975) or to secondary production by tumour-stimulated fibroblasts (Naito et al, 1984;Yamamoto et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach

Niitsu

Ito²,

Kohda³

et al. 1988

Br J Cancer

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Summary Human gastric carcinomas were tested for their immunohistochemical reactivity with anti-type I procollagen antiserum. In all specimens of scirrhous carcinomas, staining of the tumour cells was strongly positive, while in medullary carcinomas staining of the tumour cells was generally poor. These results suggest that the tumour cells in scirrhous carcinomas produce collagen in their stroma.Scirrhous carcinoma of the stomach is characterized by extensive fibrosis with sparse tumour cell infiltration in desmoplastic stroma, and clinically by the worst prognosis of any type of gastric cancer. The fibrous stroma is composed mainly of type I and type III collagens (Kohda et al., 1984; Nagi et al., 1985). Both of these are found in most normal connective tissues, but type I is more prevalent. Generally, mesenchymal cells are responsible for the synthesis and deposition of collagen in connective tissues. In an attempt to determine which cell types are responsible for the synthesis of collagen in tissue of scirrhous carcinoma, the immunohistochemical localization of procollagen type I, a precursor form of collagen type I, was investigated. Materials and methodsPurification of type I procollagen Normal human lung fibroblasts (IMR90) (Uitto et al., 1976) in the 20-30th generation with 3rd-5th passage, were grown at 37°C in culture flasks, (T 75, T 150; Corning) or roller bottles (area 490 cm2, Corning), in Dulbecco's modified Eagle medium (DMEM, Grand Island Biological), supplemented with 10% foetal calf serum and 50pgml-1 Geramycin (Schering). When the cells reached the early confluence they were washed 3 times with PBS and cultured another 24 h in serum-free DMEM containing ascorbate (75 pg ml -1) and L(2,3)3H-proline (20-40 Ci mmol -1, New England Nuclear) 4 pCi ml -1. The serum-free medium (-. 1 1) was then collected and cooled on ice, and to it were added various protease inhibitors (Uitto et al., 1976) to give the following final concentrations: 25 mm disodium ethylene diaminetetraacetate (EDTA, Baker); 10 mm N-ethylmaleimide (NEM, Sigma); 1.0 mm phenylmethylsulfonyl-fluoride (PMSF, Sigma) and 1 mm p-aminobenzamide-HCI (Sigma). Proteins in the medium were precipitated by adding 176mgml-1 ammonium sulphate (Baker) with stirring overnight at 4°C. The precipitate was centrifuged at 30,000g for 30min to remove supernatant. The pellet was then dissolved in 20 ml of ice-cold of 0.1 M Tris HCI buffer containing 0.4 M NaCl, pH7.5, and was centrifuged at 30,000g for 30min. The supernatant was dialyzed against 0.1 M Tris HCI buffer, pH7.8, containing 2M urea, 2.5mm EDTA (starting buffer A) at 4°C for overnight, prior to the application to a DEAE Sephacel column (1.6 x 1Ocm) which had been equilibrated with the starting buffer A.Chromatography was carried out with a linear salt gradient prepared with 150ml of the starting buffer A and equal amounts of the same buffer containing 0.2M NaCl. Small portions (200 ul) of each fraction (2.5 ml) from the column were mixed with Hydrofluor (National Diagnostics) and counted in a...

show abstract

Inappropriate production of collagen and prolyl hydroxylase by human breast cancer cells in vivo

Cited by 43 publications

References 17 publications

Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts

Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts

Patterns of Stromal Elements in an Implanted Ureteric Transitional Cell Carcinoma

Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach

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