Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer

Maemura, Michio; Iino, Yuichi; Yokoe, Takao; Horiguchi, Jun; Takei, Hiroyuki; Koibuchi, Yukio; Horii, Y; Takeyoshi, Izumi; Ohwada, Susumu; Morishita, Yasuo

doi:10.1016/s0304-3835(98)00014-7

Cited by 39 publications

(30 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also in breast cancer, disruption of the c-Met pathway has been shown to contribute to worse prognosis (20,37) and confer resistance to endocrine therapy or trastuzumab treatment (38)(39)(40). In addition to c-Met, its ligand HGF is also suggested to be an independent prognostic parameter for breast cancer (41,42). Hence, it was of great interest to us to understand the significance of MACC1 as a candidate regulator of the HGF/c-Met cascade in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Differential role of MACC1 expression and its regulation of the HGF/c-Met pathway between breast and colorectal cancer

Sueta

Yamamoto

Yamamoto-Ibusuki

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. The newly identified gene, metastasis-associated in colon cancer 1 (MACC1), is suggested to be a transcriptional regulator of c-Met, leading to cancer progression in colorectal cancer. To date however, little is known of the role of MACC1 in breast cancer. In a series of 300 breast cancer patients, we analyzed the association of MACC1 mRNA and protein expression with breast cancer survival using Cox proportional hazard models. In an in vitro study, we evaluated activities of c-Met protein after transfection with a MACC1-harboring plasmid as well as the binding ability of MACC1 to the c-Met promoter using a chromatin immunoprecipitation (ChIP) assay. In survival analyses, reduced MACC1 expression was associated with patient mortality. MACC1 expression was an independent prognostic factor in multivariate analysis. In the cell lines tested, MACC1 expression was much higher in colorectal than in breast cancer cells. After cells were transfected with MACC1, c-Met expression was not induced in MCF7 cells, whereas corresponding c-Met expression was upregulated in SW480 cells. Further, SW480 cells transfected with MACC1 showed enhanced migratory ability, whereas in MDA-MB-231 cells, transfection of MACC1 had no impact on this ability. In ChIP assay, the binding of MACC1 to the c-Met promoter was suggested in SW480 cells, but not in MCF7 cells. In conclusion, our findings provide some novel insights into the role of MACC1 in breast cancer, indicating that it plays different roles in breast and several other cancers. There is a possibility that MACC1 does not modulate the transcriptional role of c-Met signaling in breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential role of MACC1 expression and its regulation of the HGF/c-Met pathway between breast and colorectal cancer

Sueta

Yamamoto

Yamamoto-Ibusuki

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Activation of the c-Met pathway, indicated by p-Met levels, tends to increase with disease progression (17)(18)(19)(20)(21)(22), and tends to be higher in liver metastases than in the primary tumor site. In this study, ficlatuzumab inhibition of p-Met and subsequent downstream signaling was investigated in patients with advanced tumors with liver metastases accessible to repeat biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…c-Met pathway activation has been associated with progression from primary to metastatic disease, particularly with liver metastasis (17)(18)(19)(20)(21)(22). Serum HGF levels are elevated in patients with breast cancer with malignant liver lesions (18), and have been correlated with liver metastases versus metastases at other sites (21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Pharmacodynamic/Pharmacokinetic Study of Ficlatuzumab in Patients with Advanced Solid Tumors and Liver Metastases

Tabernero

Elez

Herranz

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: This study evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics, and antitumor activity of ficlatuzumab, a humanized hepatocyte growth factor (HGF) inhibitory monoclonal antibody, as monotherapy in patients with advanced solid tumors and liver metastases. Patients and Methods: Patients with p-Met (phosphorylated c-Met)–positive tumors enrolled in three dose-escalation cohorts, receiving ficlatuzumab 2, 10, or 20 mg/kg once per 14-day cycle. Pharmacodynamic changes in liver tumor biopsies and serum, pharmacokinetics, safety, and clinical activity were assessed. Results: No dose-limiting toxicities occurred in the 19 patients enrolled (n = 6, 2 mg/kg; n = 7, 10 mg/kg; n = 6, 20 mg/kg). The most frequent diagnosis was colorectal cancer (n = 15; 79%). The most common treatment-emergent adverse events were asthenia, peripheral edema, hepatic pain (32% each), and cough (26%). Laboratory abnormalities of decreased serum albumin were present in all patients. Ficlatuzumab at 20 mg/kg lowered median levels of tumor p-Met (−53%), p-ERK (−43%), p-Akt (−2%), and increased median HGF levels (+33%), at the last on-study time point relative to baseline. Mean serum HGF levels increased with ficlatuzumab dose and number of treatment cycles. Ficlatuzumab exhibited linear pharmacokinetics and long terminal half-life (7.4–10 days). Best overall response was stable disease in 28% of patients, including 1 patient with pancreatic cancer with stable disease >1 year. Conclusions: Ficlatuzumab exhibited good safety/tolerability and demonstrated ability to modulate the HGF/c-Met pathway and downstream signaling in the tumor in patients with advanced solid tumors. Safety, pharmacodynamic, and pharmacokinetic data for ficlatuzumab confirmed the recommended phase II dose of 20 mg/kg once per 14-day cycle. Clin Cancer Res; 20(10); 2793–804. ©2014 AACR.

show abstract

“…The serum level of HGF/SF has been found to be markedly increased in breast cancer patients with liver metastases [15,[25][26][27] , although it is unclear whether this phenomenon is tumor-related, based on the impaired clearing function of the liver, or due to ongoing repair mechanisms for regeneration of the organ. A better understanding of the role of HGF/SF in this context would be helpful for the development of diagnostic or therapeutic strategies for patients with breast cancer liver metastases.…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Hepatocyte Growth Factor/Scatter Factor in Patients with Liver Metastases from Breast Cancer

Eichbaum¹,

Rossi²,

Kaul³

et al. 2007

Tumor Biol

View full text Add to dashboard Cite

Objective: Recent studies have shown that the pleiotropic cytokine hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-Met play major roles in the malignant progression of numerous tumors. For patients with breast cancer liver metastases, increased serum levels of HGF/SF have been reported. We studied the relationship between the clinical course of the disease and the serum levels of HGF/SF in such patients. Methods: We examined 51 patients treated for breast cancer liver metastases. Serum concentrations of HGF/SF were measured before each therapy cycle and compared to the corresponding tumor marker levels. Results: Mean serum levels of HGF/SF in patients with liver metastases were increased above the reported reference levels of primary breast cancer patients. Serum levels of HGF/SF were correlated with tumor marker levels in a logarithmic relation (r = 0.47, p < 0.001). In some cases serum concentrations of HGF/SF changed similarly to the course of the corresponding tumor markers. Conclusions: Serum levels of HGF/SF are associated with the clinical course of metastatic breast cancer patients with liver metastases. Further studies are required to clarify the potential value of the HGF/SF serum concentration as a tumor marker. HGF/SF and its receptor c-Met should be further evaluated as therapeutic targets.

show abstract

Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer

Cited by 39 publications

References 23 publications

Differential role of MACC1 expression and its regulation of the HGF/c-Met pathway between breast and colorectal cancer

Differential role of MACC1 expression and its regulation of the HGF/c-Met pathway between breast and colorectal cancer

A Pharmacodynamic/Pharmacokinetic Study of Ficlatuzumab in Patients with Advanced Solid Tumors and Liver Metastases

Serum Levels of Hepatocyte Growth Factor/Scatter Factor in Patients with Liver Metastases from Breast Cancer

Contact Info

Product

Resources

About