Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19

Mantovani, Liliana; Miotti, Silvia; Ménard, Sylvie; Canevari, Silvana; Raspagliesi, Francesco; Bottini, C.; Bottero, Federica; Colnaghi, M. I.

doi:10.1016/0959-8049(94)90257-7

Cited by 107 publications

(81 citation statements)

References 18 publications

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“…103 These newer conjugates are capable of concentrating at pathologic sites as non-invasive probes for diagnostic imaging and do not suffer from problems associated with ligands such as antibodies, which among other factors, can be immunogenic and expensive to produce. 98 Finally, the sensitivity of GPI links to specific phospholipases, such as phospholipase C and D, which are abundant in plasma, may also provide a means to control FRa level at the cell surface 64 or to develop sensitive biomarker assays of the soluble protein for early detection, 66,108 as has recently been described for 2 folate-related disorders. 109,110 Implications and future directions Given the data, it is unknown whether perturbations in FOLR1 gene expression initiate neoplasia, or if neoplasia is a precondition for elevated FOLR1 expression.…”

Section: Exploitation Of Fra For Therapeutic and Diagnostic Potentialmentioning

confidence: 99%

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Kelemen

2006

Intl Journal of Cancer

440

340

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Folate receptor a (FRa) is a membrane-bound protein with high affinity for binding and transporting physiologic levels of folate into cells. Folate is a basic component of cell metabolism and DNA synthesis and repair, and rapidly dividing cancer cells have an increased requirement for folate to maintain DNA synthesis, an observation supported by the widespread use of antifolates in cancer chemotherapy. FRa levels are high in specific malignant tumors of epithelial origin compared to normal cells, and are positively associated with tumor stage and grade, raising questions of its role in tumor etiology and progression. It has been suggested that FRa might confer a growth advantage to the tumor by modulating folate uptake from serum or by generating regulatory signals. Indeed, cell culture studies show that expression of the FRa gene, FOLR1, is regulated by extracellular folate depletion, increased homocysteine accumulation, steroid hormone concentrations, interaction with specific transcription factors and cytosolic proteins, and possibly genetic mutations. Whether FRa in tumors decreases in vivo among individuals who are folate sufficient, or whether the tumor's machinery sustains FRa levels to meet the increased folate demands of the tumor, has not been studied. Consequently, the significance of carrying a FRa-positive tumor in the era of folic acid fortification and widespread vitamin supplement use in countries such as Canada and the United States is unknown. Epidemiologic and clinical studies using human tumor specimens are lacking and increasingly needed to understand the role of environmental and genetic influences on FOLR1 expression in tumor etiology and progression. This review summarizes the literature on the complex nature of FOLR1 gene regulation and expression, and suggests future research directions. ' 2006 Wiley-Liss, Inc.

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Section: Exploitation Of Fra For Therapeutic and Diagnostic Potentialmentioning

confidence: 99%

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Kelemen

2006

Intl Journal of Cancer

440

340

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“…The fixed cells were reacted with the primary antibodies and then followed by rhodamine-labelled anti-mouse IgG second antibody. FBP-specific monoclonal antibody MOv19 was a gift from MI Colnagh (Mantovani et al, 1994). Immunofluorescent images of cells were monitored under a laser scanning confocal microscope (Bio-Rad) at Â 600 magnification.…”

Section: Confocal Image Analysismentioning

confidence: 99%

Reduced expression of small GTPases and hypermethylation of the folate binding protein gene in cisplatin-resistant cells

Liang

et al. 2004

Br J Cancer

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Reduced accumulation of cisplatin is the most consistent feature seen in cisplatin-resistant (CP-r) cells that are cross-resistant to other cytotoxic compounds, such as methotrexate. In this report, defective uptake of a broad range of compounds, including As 5 þ and 73 As 3 þ , was detected in CP-r human hepatoma and epidermal carcinoma cells that we have previously shown are defective in fluidphase endocytosis. Downregulation of several small GTPases, such as rab5, rac1, and rhoA, which regulate endocytosis, was found in CP-r cells. However, expression of an early endosomal protein and clathrin heavy chain was not changed, suggesting that the defective endocytic pathway is clathrin independent. Reduced expression of the cell surface protein, folate-binding protein (FBP), which is a carrier for the uptake of MTX, was also observed in the CP-r cells by confocal immunofluorescence microscopy and RealTime PCR. Reactivation of the silenced FBP gene in the CP-r cells by a DNA demethylation agent, 2-deoxy-5-aza-cytidine (DAC) demonstrates that hypermethylation occurred in the CP-r cells. The uptake of [

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“…The low capacity is due to endocytosis of the receptor that has to return to the cell surface in order to function. Expression is limited to specific tissues and is expressed in a characteristic distribution, for example, on syncytiotrophoblastic cells of the placenta and the proximal convoluted tubule of the kidney (Weitman et al, 1992;Mantovani et al, 1994). However, FRa has been reported to be highly expressed in some malignancies: in 90% of non-mucinous epithelial ovarian cancers (Toffoli et al, 1997) and in 72% of malignant mesotheliomas (Bueno et al, 2001).…”

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confidence: 99%

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

et al. 2010

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BACKGROUND: The standard treatment of choice for malignant pleural mesothelioma is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor. This study investigates the response to pemetrexed in a panel of eight mesothelioma cell lines and the clinical outcome for patients treated with pemetrexed in relation to folate receptor alpha (FRa). METHODS: Cell lines were treated with pemetrexed to determine the concentration that reduced growth to 50% (GI 50 ). FRa expression was determined by western blotting and that of FRa, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) by real-time quantitative RT -PCR. Immunohistochemistry for FRa was carried out on 62 paraffin-embedded samples of mesothelioma from patients who were subsequently treated with pemetrexed. RESULTS: A wide range of GI 50 values was obtained for the cell lines, H2452 cells being the most sensitive (GI 50 22 nM) and RS5 cells having a GI 50 value greater than 10 mM. No FRa protein was detected in any cell line, and there was no relationship between sensitivity and expression of folate transporters. FRa was detected in 39% of tumour samples, generally in a small percentage of cells. There was no correlation between the presence of FRa and the outcome of pemetrexed treatment, and no significant difference between histological subtypes. CONCLUSION: Response to treatment with pemetrexed does not depend on the presence of FRa.

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Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19

Cited by 107 publications

References 18 publications

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Reduced expression of small GTPases and hypermethylation of the folate binding protein gene in cisplatin-resistant cells

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

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