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Hematogenous Metastasis in Gastric Cancer Requires Isolated Tumor Cells and Expression of Vascular Endothelial Growth Factor Receptor-1
Abstract
Purpose: Recent studies of cancer metastasis have focused on the role of premetastatic gene expression and circulating tumor cells. We did a blind prospective study in gastric cancer to assess the significance of isolated tumor cells (ITC) and to test the hypothesis that vascular endothelial growth factor receptor-1 (VEGFR-1) is expressed within the bone marrow at tumor-specific, premetastatic sites. Experimental Design: Both bone marrow and peripheral blood samples from 810 gastric cancer patients were collected at the Central Hospital, National Cancer Center (Tokyo, Japan). The samples were transferred to Kyushu University Hospital (Beppu, Japan) where they were analyzed by quantitative real-time reverse transcription-PCR for three epithelial cell markers, carcinoembryonic antigen, cytokeratin-19, and cytokeratin-7, as well as VEGFR-1. Results: ITCs were observed in peripheral blood and bone marrow even in early stages of gastric cancer. The frequency of ITC in bone marrow was significantly associated with the stage of disease by ANOVA (P < 0.01). Gastric cancer metastasized when ITCs were observed in the presence of VEGFR-1. In the 380 patients who were ITC negative and showed low VEGFR-1 expression, synchronous (at the time of surgery) and heterochronous (recurrent) metastases were not observed. Conclusions: ITCs circulate even in early stages of disease. Furthermore, elevated expression of VEGFR-1 facilitates the establishment of hematogenous metastases in gastric cancer. This study indicates that the simultaneous presence of ITC and VEGFR-1 expression at premetastatic sites is clinically significant for disease progression.
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“Previous literature has demonstrated that gastric tumors may recur a few years after resection even if a curative R0 according to postoperative pathological diagnosis 26, 27.”
From Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer (2017) · cites this paper as [26]
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Metadata
- Authors
- Mimori, K., Fukagawa, T., Kosaka, Y., Kita, Y., Ishikawa, K., Etoh, T., Iinuma, H., Sasako, M., & Mori, M.
- Affiliations
- Medical Institute of Bioregulation, Kyushu University (JP)
- Teikyo University (JP)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-05-01
- Volume
- 14
- Issue
- 9
- Pages
- 2609-2616
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2142670764
- Cited by
- 71
- References
- 32
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- gastric cancer, isolated tumor cells, VEGFR1, hematogenous metastasis, bone marrow, circulating tumor cells, carcinoembryonic antigen, cytokeratin 19, CK7, disease stage
- MeSH terms
- Adult, Aged, Aged, 80 and over, Bone Marrow, Carcinoembryonic Antigen, Female, Humans, Liver Neoplasms, Lung Neoplasms, Male, Middle Aged, Neoplastic Cells, Circulating, Neoplasm Metastasis, Prospective Studies, Stomach Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Vascular Endothelial Growth Factor Receptor-1, Keratin-19, Keratin-7
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