Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation.

Vostrejs, Michael; Moran, Patrick L.; Seligman, Paul A.

doi:10.1172/jci113591

Cited by 101 publications

(44 citation statements)

References 24 publications

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“…It has been demonstrated that transferrin synthesis by SCLC acts as an autocrine regulator of cellular proliferation (Vostrejs et al, 1988). Immunohistochemical staining for transferrin receptor, which is needed for internalization of transferrin and iron, has been used most extensively for measuring the proliferation rate of cells and is thought to be of some prognostic value in several types of malignant tumours.…”

Section: Discussionmentioning

confidence: 99%

Soluble and cell-associated transferrin receptor in lung cancer

Dowlati

Loo²,

Bury³

et al. 1997

Br J Cancer

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Summary The expression of transferrin receptor (TfR) has been identified in many malignant tumours. In lung cancer, lymphoma and breast cancer, it has been shown that the expression of TfR correlates with tumour differentiation, probably implying some prognostic value. A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs. Based on these data we examined the utility of measuring sTfR in the serum and bronchoalveolar lavage (BAL) fluid of patients with lung cancer (n = 32) and patients with chronic obstructive pulmonary disease (n = 22). BAL fluid was centrifuged to separate the supernatant from the cellular component. Cells were lysed in a detergent and cell-associated TfR was measured by enzyme-linked immunosorbent assay (ELISA) and expressed as ng 106 cells in this cellular component. There was no difference in serum sTfR between the cancer and chronic obstructive pulmonary disease (COPD) groups. A higher level of cell-associated TfR was found in BAL of non-small-cell lung cancer patients than in COPD patients (P = 0.01). The calculated number of TfR molecules per cell in BAL correlated positively with the percentage of macrophages in BAL (P < 0.0001), suggesting that cell-associated TfR in BAL originates primarily from macrophages in this fluid. No correlation existed between BAL cellassociated TfR and tumour size, nodal status, the presence of metastases and serum sTfR. BAL cell-associated TfR was negatively correlated with BAL supernatant neuron-specific enolase (NSE) (P = 0.01). A combination of BAL supernatant NSE and cell-associated TfR detected lung cancer with a sensitivity of 91%, a specificity of 59% and positive and negative predictive values of 81% and 71% respectively. In conclusion, BAL cell-associated TfR may help in the differential diagnosis of lung cancer vs pneumonia.Keywords: lung neoplasm; transferrin receptor; bronchoalveolar lavage Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). Immunohistochemical staining for TfR has been used most extensively for measuring the proliferation rate of cells and is thought to be of some prognostic value in several types of malignant tumours (Faulk et al, 1980;Habelshaw et al, 1983;Wrba et al, 1986). It has also been demonstrated that TfR expression, detected by the monoclonal antibody OKT9, is correlated in pulmonary adenocarcinoma with the degree of histological differentiation, the degree of nuclear atypia and mitotic index and is thus important in prognosis of these malignant tumours (Kondo et al, 1990). A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs (Chitambar et al, 1989). Furthermore, it has recently been demonstrated that bronchoalveolar lavage (BAL) fluid is a suitable place to measure certain markers for lung cancer (De Diego et al, 1991;Dowlati et al, 1996).Based on these preliminary data we investigat...

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Section: Discussionmentioning

confidence: 99%

Soluble and cell-associated transferrin receptor in lung cancer

Dowlati

Loo²,

Bury³

et al. 1997

Br J Cancer

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“…Transferrin is considered to be an conditioned medium; rO, BC47 supplemented with 10% conditioned medium and anti-transferrin antibody (20 ,ug ml-'); A, BC47 supplemented with anti-human IgG; and *, KU7 supplemented with anti-transferrin antibody (20 jg ml-') autocrine regulator of cell proliferation in malignant tumour cells, where it may also be largely responsible for acquisition of serum independence (Vostrejs et al, 1988;Shapiro and Wagner, 1989). Growth factors exert their mitogenic effect by interaction with specific cell surface receptors on responsive cells.…”

Section: Discussionmentioning

confidence: 99%

“…Specialized cellular proliferation may be limited by insufficient delivery of transferrin-bound iron from plasma during situations when iron is being withheld from the circulation. To evade the difficulty of obtaining iron, certain malignant cells have the ability to produce the 'transferrin-like' substance (Kitada and Hays, 1985;Morrone et al, 1988;Dittman and Petrides, 1991;Gruber et al, 1993) as well as native serum transferrin (Vostrejs et al, 1988;Vandewalle et al, 1989;Ohkawa et al, 1990;Stackpole et al;. It could be hypothesized, therefore, that the capability of a specific subset of human bladder carcinomas to synthesize transferrin and/or a 'transferrin-like' substance might provide a source of available iron to support localized proliferation of bladder carcinoma cells in vivo in areas not well vascularized.…”

Section: Discussionmentioning

confidence: 99%

Autocrine growth induced by transferrin-like substance in bladder carcinoma cells

Tanoguchi

Tachibana²,

Murai³

1997

Br J Cancer

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Summary Ample evidence confirms that certain cancer cells have the capacity to produce multiple peptides as growth factors and that expression of their receptor may act in tumour cell paracrine and/or autocrine loop mechanisms, either by extracellular release of the growth factor or by the tumour itself. To study the possibility of an autocrine growth mechanism in bladder carcinoma, we investigated the ability of various bladder carcinoma cell lines to proliferate in serum-free medium. A rat bladder carcinoma cell line, BC47, demonstrated exponential and density-dependent growth in serum-free medium. Furthermore, conditioned medium from BC47 cells induced growth-stimulating activity for BC47 cells themselves. Purification and further characterization of this activity was performed by chromatographic methods, SDS-PAGE and N-terminal amino acid analysis. Finally, we have identified that a transferrin-like 70-kDa protein is found to be the main growth-promoting factor in this conditioned medium. In addition, specific antibodies against transferrin and the transferrin-receptor inhibit the in vitro growth of this cell line. Our data suggest that this transferrin-like factor possibly acts as an autocrine growth factor for cancer cells.Keywords: autocrine growth factor; bladder carcinoma; rat bladder carcinoma cell line (BC47); serum-free culture; transferrinThe relatively autonomous nature of malignant cells has been known for many years, i.e. they require fewer exogeneous growth factors for optimal growth than do their counterparts. To explain this phenomenon, it has been suggested that cells could become malignant by the endogeneous production of polypeptide growth factors acting on their producer cells via functional external receptors, allowing phenotypic expression of the peptide by the same cell that produces it. This process has been termed 'autocrine secretion' (Sporn and Todaro, 1980; Sporn and Roberts, 1985). There is now much circumstantial and direct evidence to support the original hypothesis. Many types of tumour cells release polypeptide growth factors into their conditioned medium when grown in cell culture, and these same tumour cells often possess functional receptors for the released peptide.The presence of either serum components or substances such as hormones and growth factors is essential to maintain cells in culture. In analysing the regulatory mechanism of growth factors, the importance of cells that can proliferate in chemically defined, serum-free medium without supplements is increasing, because such cells are likely to synthesize factors with growth-stimulating activity (Messing et al, 1984;Matsuda et al, 1989) that can be isolated easily in the absence of extrinsic growth factors. Recently, it was demonstrated that bladder carcinoma cells were able to secrete a variety of autocrine factors, such as tumour-derived adhesion factor (Akaogi et al, 1994) and granulocyte colony-stimulating factor (Tachibana et al, 1995). The present study was undertaken to investigate the ability of various bla...

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“…Transferrin is also present in placenta, kidney, mammary glands, stomach, immune system cells, heart, lungs and tumor cells in detectable amounts [74][75][76][77][78]. The expression level of Trf receptor on the surface of proliferating cells is higher when compared to the absent or rare expression of Trf receptor on the surface of resting cells [79].…”

Section: Salivary Transferrin As a Molecular Markermentioning

confidence: 99%

Oral Cancer Biomarkers - as Powerful Diagnostic and Prognostic Tools

Ahuja¹

2016

Int.J.Curr.Microbiol.App.Sci

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Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation.

Cited by 101 publications

References 24 publications

Soluble and cell-associated transferrin receptor in lung cancer

Soluble and cell-associated transferrin receptor in lung cancer

Autocrine growth induced by transferrin-like substance in bladder carcinoma cells

Oral Cancer Biomarkers - as Powerful Diagnostic and Prognostic Tools

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