CXCL1–Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow–Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma

Kasashima, Hiroaki; Yashiro, Masakazu; Nakamae, Hirohisa; Kitayama, Kisyu; Masuda, Go; Kinoshita, Haruhito; Fukuoka, Tatsunari; Hasegawa, Tsuyoshi; Nakane, Takahiko; Hino, Masayuki; Hirakawa, Kosei; Ohira, Masaichi

doi:10.1016/j.ajpath.2016.07.024

Cited by 40 publications

(42 citation statements)

References 38 publications

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“…As mentioned above, many studies reported that CXCL1 signaling in the tumor microenvironment was associated with tumor progression. Our present results might be explained as follows: CXCL1 secretion by gastric cancer cells occurs first and subsequently stromal cells with CXCR2 expression are recruited into the tumor microenvironment, which is consistent with our previous in vitro and in vivo findings [8]. …”

Section: Discussionsupporting

confidence: 92%

“…We previously reported that CAFs in diffuse-type gastric cancer (DGC) might originate from BM-MCs, and that CXCL1 from DGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs in vitro and in vivo [8]. CXCL1 and CXCR2 are expressed in both gastric cancer cells and stromal cells including fibroblasts and macrophages in our study.…”

Section: Discussionmentioning

confidence: 49%

“…CXCL1 and CXCR2 are expressed in both gastric cancer cells and stromal cells including fibroblasts and macrophages in our study. Previously, we reported that CXCL1 secreted from gastric cancer cells might play an important role for the migration activity of BM-MCs via CXCL1/CXCR2 signaling [8]. Therefore, we focused on CXCL1 expression in gastric cancer cells and CXCR2 expression in stromal fibroblast cells in this study.…”

Section: Discussionmentioning

confidence: 99%

“…We also observed that the stromal expression of CD271, which is one of the markers of BM-MCs, was a useful prognostic factor for gastric cancer patients [7]. Another of our studies demonstrated that chemokine (C-X-C motif) ligand 1 (CXCL1), which is produced from diffuse-type gastric cancer (DGC) cells, is closely associated with the recruitment of BM-MCs into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) of BM-MCs [8]. …”

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma

et al. 2017

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PurposeIt was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer.MethodsThe correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro.ResultsThe expression of CXCL1 in cancer cells was correlated with T invasion (T2–T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2–T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients.ConclusionThe expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma

et al. 2017

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“…The growing number of new vessels was reported to facilitate GC metastasis [73,74]. To promote angiogenesis, GC cells provide numerous angiogenic factors, including VEGF, FGF-2, CXCL1, and Ang-2, to microenvironment [75][76][77][78]. It has been noted that high level of VEGF-A contributed to endothelium-dependent angiogenesis.…”

Section: The Tumor Microenvironment and Gastric Carcinogenesismentioning

confidence: 99%

Molecular Pathogenesis of Gastric Adenocarcinoma

Kang¹,

Zhang²,

To³

2018

Stomach Disorders

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The incidence and mortality of gastric cancer (GC) rank top ive and top three, respectively, among cancers around the world. It is an intricate malignancy caused by the reciprocity of intrinsically genetic, environmental, and host-related elements. The silent property, advanced clinical characterization, and potential heterogeneity have made GC a thorny disease with a high death rate. The increasing knowledge of the abundant genetic abnormalities regarding GC will deinitely elongate the patients' survival. Scientists have been working hard to discover the myths beneath gastric tumorigenesis: novel biomarkers have been established, and cell transduction cascades have been well described. The study grouping GC into four molecular subtypes by The Cancer Genome Atlas (TCGA) broadens our horizon of GC etiologies. Knowledge regarding to the sophisticated networks in tumor microenvironment also bring new insights into the mechanisms assist GC development. In the future, people will strive for translating more research achievements into clinical utility. Successful translational medicine will lead to new methods for early GC diagnosis and precise medical strategies for individuals.

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Chemokine signaling in cancer-stroma communications

Singh

Gray

2021

J. Cell Commun. Signal.

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Cancer is a multi-faceted disease in which spontaneous mutation(s) in a cell leads to the growth and development of a malignant new organ that if left undisturbed will grow in size and lead to eventual death of the organism. During this process, multiple cell types are continuously releasing signaling molecules into the microenvironment, which results in a tangled web of communication that both attracts new cell types into and reshapes the tumor microenvironment as a whole. One prominent class of molecules, chemokines, bind to specific receptors and trigger directional, chemotactic movement in the receiving cell. Chemokines and their receptors have been demonstrated to be expressed by almost all cell types in the tumor microenvironment, including epithelial, immune, mesenchymal, endothelial, and other stromal cells. This results in chemokines playing multifaceted roles in facilitating context-dependent intercellular communications. Recent research has started to shed light on these ligands and receptors in a cancer-specific context, including cell-type specificity and drug targetability. In this review, we summarize the latest research with regards to chemokines in facilitating communication between different cell types in the tumor microenvironment.

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CXCL1–Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow–Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma

Cited by 40 publications

References 38 publications

Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma

Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma

Molecular Pathogenesis of Gastric Adenocarcinoma

Chemokine signaling in cancer-stroma communications

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