Growth factor content in normal and benign ovarian tumours

Owens, Owen; Leake, Robin

doi:10.1016/0028-2243(92)90155-r

Cited by 12 publications

(6 citation statements)

References 9 publications

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“…Transforming growth factor alpha has been associated with ovarian cancer [44,45] and may act as an autocrine growth factor to induce cell proliferation in both normal and tumorigenic OSE [46,47]. The data presented on normal bovine ovaries and human tumor tissue extend the previous observations with normal human and rodent ovaries with immunocytochemistry and in situ hybridization [27-33, 46, 47].…”

Section: Discussionsupporting

confidence: 84%

Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1

Doraiswamy

Parrott

Skinner

2000

Biology of Reproduction

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Greater than 95% of ovarian cancers originate in the epithelial cells on the surface of the ovary. The current study investigates the expression and action of transforming growth factor alpha (TGFalpha) in ovarian surface epithelium (OSE) and the underlying stroma in both normal and tumorigenic ovarian tissues. Normal bovine ovaries are used in the current study as a model system to investigate normal OSE functions. Transforming growth factor alpha and its receptor, the epidermal growth factor receptor (EGFR), were detected in the OSE from normal ovaries by immunocytochemistry (ICC). Ovarian stromal tissue also contained reduced but positive TGFalpha and EGFR immunostaining. To examine TGFalpha and EGFR gene expression, RNA was collected from normal bovine OSE and ovarian stromal cells. The TGFalpha and EGFR transcripts were detected in both fresh and cultured OSE and stromal cells by a sensitive quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay. Transforming growth factor alpha gene expression was found to be high in freshly isolated OSE, but low in freshly isolated stroma. In contrast, EGFR expression was higher in the stroma compared to the OSE. Both the ICC and QRT-PCR indicate that normal OSE express high levels of TGFalpha in vivo and in vitro. In vitro, normal ovarian stromal cells develop the capacity to express high levels of EGFR. Human ovarian tumors from stage II, stage III, and stage IV ovarian cancer cases were found to express TGFalpha and EGFR protein in the epithelial cell component of the tumor by ICC analysis. The stromal cell component of human ovarian tumors contained little or no TGFalpha/EGFR immunostaining. Observations suggest that tumor progression may in part require autocrine stimulation of the epithelia. Transforming growth factor alpha was found to stimulate the growth of normal bovine OSE and stroma cells to the same level as epidermal growth factor. Two ovarian cancer cell lines, SKOV3 and OCC1, were also stimulated to proliferate in response to TGFalpha. Transforming growth factor alpha was also found to stimulate the expression of two growth factors previously shown to be produced by OSE. Transforming growth factor alpha stimulates both kit ligand/stem cell factor and keratinocyte growth factor production by OSE. The effect of hormones on TGFalpha and EGFR expression by the OSE was also examined. Human chorionic gonadotropin stimulated TGFalpha expression, but not FSH. Both hCG and FSH stimulated EGFR expression by OSE. Combined observations suggest a role of systemic hormones and a locally produced growth factor, TGFalpha, in OSE biology. Insight is also provided into how the OSE may develop abnormal growth characteristics involved in the onset and progression of ovarian cancer.

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Section: Discussionsupporting

confidence: 84%

Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1

Doraiswamy

Parrott

Skinner

2000

Biology of Reproduction

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“…We can discuss our data qualitatively or quantitatively. Qualitatively, our detection of TGF-· in the sera of controls and ovarian cancer patients is consistent with the radioimmunoassay (RIA) results of Owens and Leake [16] who found TGF-· present in the tissue of approximately 84% of normal ovaries, and with the follow-up study of Owens et al [17] and with Kommoss et al [18] who performed immunohistochemistry on frozen tumor tissue. Only 6 of our 36 ascites samples had detectable TGF-· levels.…”

Section: Discussionsupporting

confidence: 76%

Transforming Growth Factor-Alpha Levels in the Serum and Ascites of Patients withAdv anced Epithelial Ovarian Cancer

Saltzman¹,

Hartenbach²,

Carter³

et al. 1999

Gynecol Obstet Invest

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A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-α (TGF-α) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-α was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-α, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-α might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-α values versus controls and the primary study group approached significance. TGF-α was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.

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“…However, another study has shown TGF-ot in the primary follicles, granulosa, and theca cell layers, as well as in small and large luteal cells (Chegini and Williams 1992). In addition, TGF-c~ has been measured in normal human ovaries (Owens and Leake 1992). TGF-o~ immunoreactivity in the resting and lactating mammary gland has not been described before, but TGF-o~ has been measured in human milk (Okada et al 1991).…”

Section: Discussionmentioning

confidence: 98%

Immunolocalization of transforming growth factor alpha in normal human tissues

Christensen

Poulsen

1996

Histochem Cell Biol

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Transforming growth factor alpha (TGF-alpha) is a polypeptide with well-characterized growth promoting properties. The effects are exerted through the epidermal growth factor receptor (EGF receptor), which is present on many different kinds of cells. The growth factor was initially shown to induce anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly localized adjacent to the nucleus, usually on the luminal aspect, corresponding to the localization of the Golgi complex. The latter staining pattern was seen predominantly in secretory epithelial cells. The present study thus confirms previous studies and elaborates new localizations of TGF-alpha in normal human tissues by investigating a broad spectrum of tissues in detail.

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Growth factor content in normal and benign ovarian tumours

Cited by 12 publications

References 9 publications

Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1

Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1

Transforming Growth Factor-Alpha Levels in the Serum and Ascites of Patients withAdv anced Epithelial Ovarian Cancer

Immunolocalization of transforming growth factor alpha in normal human tissues

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