Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies

Baiocchi, G.; Talpaz, Moshe; Gutterman, Jordan U.; Kurzrock, Razelle; Kavanagh, John J.; Wharton, J. Taylor

doi:10.1002/1097-0142(19910215)67:4<990::aid-cncr2820670422>3.0.co;2-8

Cited by 91 publications

(51 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abnormally high CSF1R expression has been associated with aggressive behavior and poor outcome in a variety of malignancies, including breast, 22,23 endometrial, 24,25 ovarian, 26,27 and prostate cancers. 28 The follow-up time in this series is still relatively short to allow a meaningful evaluation of the prognostic value of CSF1R overexpression in renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 Concomitant expression of CSF1R and CSF1 was also observed in endometrial cancer cells and it is absent in the adjacent normal tissue. 24,25 Finally, it has been shown in uterine cervical carcinomas that the CSF1/CSF1R-signaling pathway is involved in enhanced survival and invasion of cancer cells via an autocrine mechanism. 30 Our finding of increased CSF1R expression at both the mRNA and protein level in most clear cell renal cell carcinomas suggests that tumor cells may be hypersensitive even to normal CSF1 levels, presumably resulting in decreased apoptosis and increased ability to invade.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas

et al. 2009

View full text Add to dashboard Cite

Renal cell carcinomas comprise a heterogeneous group of tumors. Of these, 80% are clear cell renal cell carcinomas, which are characterized by loss of 3p, often with concomitant gain of 5q22qter. Although VHL is considered the main target gene of the 3p deletions, none has been identified as the relevant target gene for the 5q gain. We have studied 75 consecutive kidney tumors and paired normal kidney samples to evaluate at the genomic and expression levels the tyrosine kinase genes CSF1R and PDGFRB as potential targets in this region. Our findings show that RNA expression of CSF1R, but not of PDGFRB, was significantly higher in clear cell renal cell carcinomas than in normal tissue samples, something that was corroborated at the protein level by immunohistochemistry. The CSF1R staining pattern in clear cell renal cell carcinomas was clearly different from that observed in other renal cell carcinomas, suggesting its potential usefulness in differential diagnosis. FISH analysis demonstrated whole chromosomal gain and relative CSF1R/PDGFRB copy number gain in clear cell renal cell carcinomas, which might contribute to CSF1R overexpression. Finally, one polymorphism and two novel mutations were identified in CSF1R in clear cell renal cell carcinoma patients. Our data allow us to conclude that CSF1R plays a relevant role in clear cell renal cell carcinoma carcinogenesis and raise the possibility that CSF1R may represent a future valuable therapeutic target in these patients. Keywords: renal cell carcinoma; CSF1R oncogene; mutation; overexpression Renal cell carcinomas comprise a heterogeneous group of tumors that represent about 3% of all malignancies in adults in the Western countries. 1 Clear cell renal cell carcinomas, which represent about 80% of all kidney tumors, are characterized by the loss of the short arm of chromosome 3 (3p), often with a concomitant gain of 5q22qter as the result of an unbalanced 3p;5q translocation. 2 Several genes have been presented as the targets of the 3p deletions seen in this tumor type, with emphasis for VHL (3p25Bp26). In fact, germline mutations of VHL underlie the von Hippel-Lindau syndrome (which includes clear cell renal cell carcinoma as one of its features), whereas somatic inactivation of this gene has been demonstrated in the great majority of sporadic clear cell renal cell carcinomas. 3,4 On the other hand, no target genes have been identified for the 5q22qter gain, the second most common copy number change in clear cell renal cell carcinomas. 2,5 The colony-stimulating factor-1 receptor (CSF1R) gene located in 5q33 is a potential target for this chromosomal gain in clear cell renal cell carcinomas. CSF1R is a transmembrane tyrosine kinase receptor and the CSF1R/CSF1 receptor/ligand complex has essential physiological functions in monocyte and macrophage differentiation, embryonic implantation, placental development, and lactogenic differentiation of the human breast. 6 Codons 301 and 969 located in CSF1R exons 7 and 22, respectively, have been shown to be mutated in he...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Our observation was largely based on the RT-PCR technique, and positive RT-PCR does not mean substantial existence of proteins. Frequent co-expression of these transcripts in ovarian carcinomas, however, has been reported by other investigators (Baiocchi et al, 1991;Bauknecht et al, 1994). Taken together, it is conceivable that autocrine regulation of M-CSF may exist in some ovarian epithelial carcinomas.…”

Section: Discussionmentioning

confidence: 80%

“…It is produced by fibroblasts and endothelial cells. In addition, some kinds of carcinoma, such as ovarian epithelial carcinomas, endometrial carcinomas and mammary carcinomas, have been shown to produce M-CSF (Baiocchi et al, 1991). An abnormally high level of M-CSF is found in the sera of ovarian epithelial carcinoma patients with active disease, and the usefulness of M-CSF as a tumour marker in ovarian epithelial carcinoma has been proposed (Kacinski et al, 1989;Suzuki et al, 1993).…”

mentioning

confidence: 99%

“…These results imply that M-CSF can lead c-fins-positive cancer cells to a more malignant phenotype. The fact that a predominant number of ovarian epithelial carcinoma tissues co-express M-CSF and its receptor (Baiocchi et al, 1991;Kommoss et al, 1994) suggests that autocrine/paracrine regulation of M-CSF exists in ovarian epithelial carcinoma cells and leads them to a more malignant phenotype.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme

Yokoyama

Morishita²,

Takahashi³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Co-expression of macrophage colony-stimulating factor (M-CSF) and its receptor (c-fms) is often found in ovarian epithelial carcinoma, suggesting the existence of autocrine regulation of cell growth by M-CSF. To block this autocrine loop, we have developed hammerhead ribozymes against c-fms mRNA. As target sites of the ribozyme, we chose the GUC sequence in codon 18 and codon 27 of cfms mRNA. Two kinds of ribozymes were able to cleave an artificial c-fms RNA substrate in a cell-free system, although the ribozyme against codon 18 was much more efficient than that against codon 27. We next constructed an expression vector carrying a ribozyme sequence that targeted the GUC sequence in codon 18 of c-fms mRNA. It was introduced into TYK-nu cells that expressed M-CSF and its receptor. Its transfectant showed a reduced growth potential. The expression levels of c-fms protein and mRNA in the transfectant were clearly decreased with the expression of ribozyme RNA compared with that of an untransfected control or a transfectant with the vector without the ribozyme sequence. These results suggest that the ribozyme against GUC in codon 18 of c-fms mRNA is a promising tool for blocking the autocrine loop of M-CSF in ovarian epithelial carcinoma.

show abstract

Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines

Savarese¹,

Valinski²,

Quesenberry³

et al. 1998

Prostate

View full text Add to dashboard Cite

Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies

Cited by 91 publications

References 22 publications

CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas

CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas

Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme

Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines

Contact Info

Product

Resources

About