Serum contains a platelet-derived transforming growth factor.

We examined the ability of primary human tumour cells to secrete diffusible factors capable of stimulating anchorage independent growth of normal rat kidney fibroblast (NRK) cells. Conditioned media (CM) prepared from cells derived from 31/43 patients with adenocarcinoma of the breast, colon, ovary or lung were found to induce growth of NRK cells in soft agar. The ability of the CM to induce anchorage independent growth was enhanced in 25/35 cases by the presence of epidermal growth factor (EGF). The CM did not compete with EGF for binding to the EGF receptor site. CM from cells derived from nonmalignant effusions also supported the growth of NRK cells in soft agar. There was no significant difference in the ability of the CM derived from malignant or normal cells to support NRK colony growth. The ability of primary human tumour cells to clone in soft agar was compared to the ability of these cells to produce diffusible colony stimulating factors for NRK cells. No correlation was observed between the ability of the primary human tumour cells to clone in soft agar and their ability to induce anchorage independent growth of NRK cells. The secretion of substances with TGF like activity may be a property of many types of primary human cells.

Section: Discussionsupporting

confidence: 92%

Secretion of transforming growth factors by primary human tumour cells

Hamburger¹,

White²,

Dunn³

1985

“…Since TGF-,B mRNAs were expressed in our stromal cell cultures (Figure 5), active TGF-P could have been produced (among latent TGF-,B) by the stromal cells (Rowley, 1992b). On the other hand, the active fraction of inhibitor might consist of 'fibroblast-activated' latent TGF-P, for instance, present in the serum (Childs et al, 1982;Antonelli-Orlidge et al, 1989). Our data show that p-EIF has several properties in common with TGF-P, including reversibility of inhibition (Hebert and Birnbaum, 1989; Kooistra et al, 1995a) and sensitivity to trypsin and reducing agents.…”

Section: Discussionmentioning

confidence: 93%

“…Most cells, including stromal cells, secrete TGF-P as a latent complex which can be activated by treatment with heat, acid or proteases such as plasmin (Lawrence et al, 1985;Rowley, 1992b). Also, commercially available sera have been shown to contain latent TGF-P (Childs et al, 1982). The expression and activation appears to be influenced by steroid hormones (Kyprianou and Isaacs, 1989;Martikainen et al, 1990), as was shown also for urogenital sinus mesenchyme (Rowley, 1992b).…”

Section: Discussionmentioning

confidence: 99%

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Kooistra

Raaij²,

Klaij³

et al. 1995

Summary The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Stromal cells from the human prostate have previously been shown to inhibit anchoragedependent as well as anchorage-independent growth of the prostatic tumour epithelial cell lines PC-3 and LNCaP. Antiproliferative activity, mediated by a diffusible factor in the stromal cell conditioned medium, was found to be produced specifically by prostatic stromal cells. In the present study the characteristics of this factor were examined. It is demonstrated that prostate stroma-derived inhibiting factor is an acid-and heat-labile, dithiothreitol-sensitive protein. Although some similarities with type beta transforming growth factor (TGF-P)-like inhibitors are apparent, evidence is presented that the factor is not identical to TGF-J3 or to the TGF-p-like factors activin and inhibin. Absence of TGF-P activity was shown by the lack of inhibitory response of the TGF-p-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated, partially purified preparations of the inhibitor. Furthermore, neutralising antibodies against TGF-PI or TGF-P2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. Using Northern blot analyses, we excluded the involvement of inhibin or activin. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.

“…Harris, personal communication), stimulates differentiation and keratinization of normal, but not transformed human bronchial epithelial cells proliferating in a chemically defined medium, in a very similar manner to TPA (Willey et al, 1984), and hence might be expected to permit the same type of selective advantage to the initiated cells and their progeny if released in chemically initiated skin. The reports that the effect of TGF-# is synergistic with EGF to promote wound repair , and that it is found in platelets (Childs et al, 1982;Assoian et al, 1983) and clotted blood serum (Childs et al, 1982) but not plasma (Childs et al, 1982), suggest that the release of TGF-f may occur as part of the natural process of wound healing following damage to blood vessels. Blood vessel damage and the release of TGF-,B would accompany the promoting stimuli of skin wounding (Hennings & Boutwell, 1980;ClarkLewis & Murray, 1978;Marks et al, 1979) and to a lesser extent deep abrasion (Argyris, 1980a), but not the non-promoting stimuli of superficial abrasion (Marks et al, 1979) or skin massage (Clark-Lewis & Murray, 1978;Marks et al, 1979).…”

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 99%

Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Parkinson¹

1985

Summary Epidermal tumourigenesis can be achieved in rodents by the application of a single subthreshold dose of a carcinogen (initiation) followed by repeated applications of a tumour promoter such as 12-0-tetradecanoyl phorbol, 13-acetate (TPA). TPA induces terminal differentiation in the majority of epidermal keratinocytes in vitro. However, transformed keratinocytes respond weakly to this terminal differentiation signal, and it is suggested that this property allows initiated cells and their progeny to obtain a selective advantage over their normal counterparts during promotion of papilloma formation by TPA.New data are reviewed which suggest that a putative wound hormone TGF-P has similar differential effects on normal and transformed epithelial cells to those of TPA. It is proposed that the release of TGF-,B from platelets following deep skin wounding may be an explanation as to why wounding is a promoting stimulus but milder forms of epidermal injury are not. Weakly promoting hyperplasiogenic agents are also discussed within the context of a selection theory of tumour promotion.