Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of gastric cancer

Ogawa, T.; Kikuchi, Shinichi; Tabuchi, Masako; Mitsui, Ema; Une, Yuta; Tazawa, Hiroshi; Kuroda, Shigetoshi; Noma, Kazuhiro; Ohara, Toshiaki; Kagawa, Shunsuke; Urata, Yasuo; Fujiwara, Toshiyoshi

doi:10.1016/j.omto.2022.04.009

Cited by 11 publications

(14 citation statements)

References 49 publications

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“…The present study reveals a strong relationship between CAFs and survival. Patients with high α-SMA and FAP expression had significantly worse RFS and DSS ( Figure 4 ), in line with previous reports in gastrointestinal surgical oncology ( 14 , 15 ). Moreover, our multivariable analyses suggested that α-SMA was an independent predictor of RFS and DSS after surgery ( Tables 3 , 4 ).…”

Section: Discussionsupporting

confidence: 91%

“…A recent review reported the association of CAFs with cancer invasion and metastasis that occurs through extracellular matrix deposition and remodeling, epithelial-mesenchymal transition in cancer cells, and secretion of growth factors supporting cancer cells ( 17 ). Furthermore, potential CAF-targeted therapeutic strategies have been suggested ( 6 , 14 – 17 ). There are ongoing clinical trials investigating the efficacy of CAF-targeted therapies combined with existing therapies ( 8 , 18 – 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…We employed a previously reported protocol for evaluating CAFs ( 14 – 16 ). First, the presence of tumor cells was confirmed by hematoxylin and eosin (H&E) staining.…”

Section: Methodsmentioning

confidence: 99%

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Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma

et al. 2023

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BackgroundCancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma.Materials and methodsA retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed.ResultsThe high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21–12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21–170; p = 0.03).ConclusionsCAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma

et al. 2023

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“…As noted earlier, cancer cells induce transcriptional alterations of p53 in CAFs relative to normal NFs [ 235 , 237 ], including in gastric cancer [ 547 ]. Gene therapy with a replicative oncolytic adenovirus-expressing wild-type p53 gene (OBP-702) against CAFs and peritoneal metastases in gastric cancer (GC) resulted in cytotoxicity to both gastric cancer cells and CAFs but not to normal gastric fibroblasts in a murine model [ 547 ].…”

Section: Cancer Stroma As a Therapeutic Targetmentioning

confidence: 97%

“…Gene therapy with a replicative oncolytic adenovirus-expressing wild-type p53 gene (OBP-702) against CAFs and peritoneal metastases in gastric cancer (GC) resulted in cytotoxicity to both gastric cancer cells and CAFs but not to normal gastric fibroblasts in a murine model [ 547 ]. It induced apoptosis and autophagy in CAFs, decreased their secretion of cancer-promoting cytokines, was synergistic with paclitaxel in inhibiting the growth of peritoneal metastases, and decreased CAFs in peritoneal metastases [ 547 ].…”

Section: Cancer Stroma As a Therapeutic Targetmentioning

confidence: 99%

Fibroblasts as Turned Agents in Cancer Progression

Wieder

2023

Cancers

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Differentiated epithelial cells reside in the homeostatic microenvironment of the native organ stroma. The stroma supports their normal function, their G0 differentiated state, and their expansion/contraction through the various stages of the life cycle and physiologic functions of the host. When malignant transformation begins, the microenvironment tries to suppress and eliminate the transformed cells, while cancer cells, in turn, try to resist these suppressive efforts. The tumor microenvironment encompasses a large variety of cell types recruited by the tumor to perform different functions, among which fibroblasts are the most abundant. The dynamics of the mutual relationship change as the sides undertake an epic battle for control of the other. In the process, the cancer “wounds” the microenvironment through a variety of mechanisms and attracts distant mesenchymal stem cells to change their function from one attempting to suppress the cancer, to one that supports its growth, survival, and metastasis. Analogous reciprocal interactions occur as well between disseminated cancer cells and the metastatic microenvironment, where the microenvironment attempts to eliminate cancer cells or suppress their proliferation. However, the altered microenvironmental cells acquire novel characteristics that support malignant progression. Investigations have attempted to use these traits as targets of novel therapeutic approaches.

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Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer

Kajiwara

Tazawa

Yamada

et al. 2022

Cancer Immunol Immunother

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Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of gastric cancer

Cited by 11 publications

References 49 publications

Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma

Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma

Fibroblasts as Turned Agents in Cancer Progression

Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer

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