Cancer-associated Fibroblasts Induce Cancer Cell Apoptosis That Regulates Invasion Mode of Tumours

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2017 Apr 4

PMID 28368418

Citations 29

Authors

G Itoh

S Chida

K Yanagihara

M Yashiro

N Aiba

M Tanaka

Affiliations

Soon will be listed here.

Abstract

In the process of cancer spreading, different modes of invasion exist. One is expansive invasion, in which a group of cancer cells gradually expands along with cancer cell proliferation. Invasion of cancer cells is also modified by their interaction with stromal cells including cancer-associated fibroblasts (CAFs). Cancer cells co-invade with CAFs, and invasion by CAFs frequently precede invasion by cancer cells, which indicates CAF-led cancer cell invasion. Here, we show that CAFs induce apoptosis in gastric cancer cells, which prevented expansive invasion by cancer cells and instead facilitated CAF-led invasion. Death receptor 4 and activation of caspase-8 in cancer cells mediated cancer cell apoptosis induced by CAFs, which was dependent on contact between cancer cells and CAFs. Apoptotic cancer cells in turn released apoptotic vesicles and stimulated invasion of CAFs. Accordingly, cancer cells followed the migrating CAFs. Treatment with a caspase inhibitor, ZVAD, or forced expression of a death domain fragment in cancer cells prevented cancer cell apoptosis induced by CAFs and increased expansive invasion by cancer cells in extracellular gel invasion assays, while the rate of cancer cell invasion led by CAFs was decreased. Death domain-fragment expression also prevented intramural invasion by gastric cancer cells in the stomach. Because CAF-led invasion is characterized by the movement of individual cancer cells away from the tumour, adequate cancer cell apoptosis may promote cancer dissemination.

Citing Articles

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.

Chen C, Liu J, Lin X, Xiang A, Ye Q, Guo J Cell Death Discov. 2024; 10(1):189.

PMID: 38649701 PMC: 11035635. DOI: 10.1038/s41420-024-01958-9.

A Vaccine against Cancer: Can There Be a Possible Strategy to Face the Challenge? Possible Targets and Paradoxical Effects.

Zefferino R, Conese M Vaccines (Basel). 2023; 11(11).

PMID: 38006033 PMC: 10674257. DOI: 10.3390/vaccines11111701.

Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway.

Yang W, Zhang S, Li T, Zhou Z, Pan J Acta Biochim Biophys Sin (Shanghai). 2022; 55(2):262-273.

PMID: 36148955 PMC: 10157546. DOI: 10.3724/abbs.2022132.

Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy.

Li X, Pi Y, Chen Y, Zhu Q, Xia B Front Oncol. 2022; 12:894744.

PMID: 35756670 PMC: 9218565. DOI: 10.3389/fonc.2022.894744.

Cytokine-driven positive feedback loop organizes fibroblast transformation and facilitates gastric cancer progression.

Cao X, Xie B, Shao Y, Lin J Clin Transl Oncol. 2022; 24(7):1354-1364.

PMID: 35303266 DOI: 10.1007/s12094-022-02777-z.

References

Turiak L, Misjak P, Szabo T, Aradi B, Paloczi K, Ozohanics O . Proteomic characterization of thymocyte-derived microvesicles and apoptotic bodies in BALB/c mice. J Proteomics. 2011; 74(10):2025-33. DOI: 10.1016/j.jprot.2011.05.023. View

Yoon N, Park M, Shigemoto T, Peltier G, Lee R . Activated human mesenchymal stem/stromal cells suppress metastatic features of MDA-MB-231 cells by secreting IFN-β. Cell Death Dis. 2016; 7:e2191. PMC: 4855669. DOI: 10.1038/cddis.2016.90. View

Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall J, Harrington K . Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007; 9(12):1392-400. DOI: 10.1038/ncb1658. View

Ciardiello C, Cavallini L, Spinelli C, Yang J, Reis-Sobreiro M, de Candia P . Focus on Extracellular Vesicles: New Frontiers of Cell-to-Cell Communication in Cancer. Int J Mol Sci. 2016; 17(2):175. PMC: 4783909. DOI: 10.3390/ijms17020175. View

Waghray M, Yalamanchili M, Dziubinski M, Zeinali M, Erkkinen M, Yang H . GM-CSF Mediates Mesenchymal-Epithelial Cross-talk in Pancreatic Cancer. Cancer Discov. 2016; 6(8):886-99. PMC: 5549011. DOI: 10.1158/2159-8290.CD-15-0947. View

Sanchez-Lopez E, Flashner-Abramson E, Shalapour S, Zhong Z, Taniguchi K, Levitzki A . Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling. Oncogene. 2015; 35(20):2634-44. PMC: 4791217. DOI: 10.1038/onc.2015.326. View

Subramaniam K, Omar I, Kwong S, Mohamed Z, Woo Y, Mat Adenan N . Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway. Am J Cancer Res. 2016; 6(2):200-13. PMC: 4859653. View

Yanagihara K, Tanaka H, Takigahira M, Ino Y, Yamaguchi Y, Toge T . Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice. Cancer Sci. 2004; 95(7):575-82. PMC: 11159459. DOI: 10.1111/j.1349-7006.2004.tb02489.x. View

Muhsin-Sharafaldine M, Saunderson S, Dunn A, Faed J, Kleffmann T, McLellan A . Procoagulant and immunogenic properties of melanoma exosomes, microvesicles and apoptotic vesicles. Oncotarget. 2016; 7(35):56279-56294. PMC: 5302914. DOI: 10.18632/oncotarget.10783. View

10.

Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M . Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene. 2014; 34(5):650-60. DOI: 10.1038/onc.2013.584. View

11.

Rhim A, Oberstein P, Thomas D, Mirek E, Palermo C, Sastra S . Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014; 25(6):735-47. PMC: 4096698. DOI: 10.1016/j.ccr.2014.04.021. View

12.

Fuyuhiro Y, Yashiro M, Noda S, Kashiwagi S, Matsuoka J, Doi Y . Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells. Br J Cancer. 2011; 105(7):996-1001. PMC: 3185946. DOI: 10.1038/bjc.2011.330. View

13.

Antwi-Baffour S . Molecular characterisation of plasma membrane-derived vesicles. J Biomed Sci. 2015; 22:68. PMC: 4532247. DOI: 10.1186/s12929-015-0174-7. View

14.

Lo Y, Lin S, Yang C, Tung J . Tandem DEDs and CARDs suggest novel mechanisms of signaling complex assembly. Apoptosis. 2014; 20(2):124-35. DOI: 10.1007/s10495-014-1054-4. View

15.

Walczak H, Haas T . Biochemical analysis of the native TRAIL death-inducing signaling complex. Methods Mol Biol. 2008; 414:221-39. DOI: 10.1007/978-1-59745-339-4_16. View

16.

Yanagihara K, Takigahira M, Tanaka H, Komatsu T, Fukumoto H, Koizumi F . Development and biological analysis of peritoneal metastasis mouse models for human scirrhous stomach cancer. Cancer Sci. 2005; 96(6):323-32. PMC: 11158165. DOI: 10.1111/j.1349-7006.2005.00054.x. View

17.

Ozdemir B, Pentcheva-Hoang T, Carstens J, Zheng X, Wu C, Simpson T . Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014; 25(6):719-34. PMC: 4180632. DOI: 10.1016/j.ccr.2014.04.005. View

18.

Alexander S, Weigelin B, Winkler F, Friedl P . Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response. Curr Opin Cell Biol. 2013; 25(5):659-71. DOI: 10.1016/j.ceb.2013.07.001. View

19.

Geraldo S, Simon A, Elkhatib N, Louvard D, Fetler L, Vignjevic D . Do cancer cells have distinct adhesions in 3D collagen matrices and in vivo?. Eur J Cell Biol. 2012; 91(11-12):930-7. DOI: 10.1016/j.ejcb.2012.07.005. View

20.

Sidani M, Wyckoff J, Xue C, Segall J, Condeelis J . Probing the microenvironment of mammary tumors using multiphoton microscopy. J Mammary Gland Biol Neoplasia. 2006; 11(2):151-63. DOI: 10.1007/s10911-006-9021-5. View