Skip to main content

Advertisement

SpringerLink
Log in

Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Surgical resection, the cornerstone of curative intent treatment for gastric adenocarcinoma, is associated with a high rate of infection-related post-operative complications, leading to an increased incidence of metastasis to the peritoneum. However, the mechanisms underlying this process are poorly understood. Lipopolysaccharide (LPS), an antigen from Gram-negative bacteria, represents a potential mechanism via induction of local and systemic inflammation through activation of Toll-like receptor (TLR). Here, we use both a novel ex vivo model of peritoneal metastasis and in vivo animal models to assess gastric cancer cell adhesion to peritoneum both before and after inhibition of the TLR4 pathway. We demonstrate that activation of TLR4 by either LPS or Gram-negative bacteria (E. coli) significantly increases the adherence of gastric cancer cells to human peritoneal mesothelial cells, and that this increased adherence is abrogated by inhibition of the TLR4 signal cascade and downstream TAK1 and MEK1/2 pathways. We also demonstrate that the influence of LPS on adherence extends to peritoneal tissue and metastatic spread. Furthermore, we show that loss of TLR4 at the site of metastasis reduces tumor cell adhesion, implicating the TLR4 signaling cascade in potentiating metastatic adhesion and peritoneal spread. These results identify potential therapeutic targets for the clinical management of patients undergoing resection for gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

References

  1. Castano-Rodriguez N, Kaakoush NO, Mitchell HM (2014) Pattern-recognition receptors and gastric cancer. Front Immunol 5:336. doi:https://doi.org/10.3389/fimmu.2014.00336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30. doi:https://doi.org/10.3322/caac.21332

    Article  PubMed  Google Scholar 

  3. Zhang XF, Huang CM, Lu HS, Wu XY, Wang C, Guang GX, Zhang JZ, Zheng CH (2004) Surgical treatment and prognosis of gastric cancer in 2,613 patients. World J Gastroenterol 10(23):3405–3408. doi:https://doi.org/10.3748/wjg.v10.i23.3405

    Article  PubMed  PubMed Central  Google Scholar 

  4. Deng J, Liang H, Wang D, Sun D, Pan Y, Liu Y (2011) Investigation of the recurrence patterns of gastric cancer following a curative resection. Surg Today 41(2):210–215. doi:https://doi.org/10.1007/s00595-009-4251-y

    Article  PubMed  Google Scholar 

  5. Riihimaki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K (2016) Metastatic spread in patients with gastric cancer. Oncotarget 7(32):52307–52316. doi:https://doi.org/10.18632/oncotarget.10740

    Article  PubMed  PubMed Central  Google Scholar 

  6. Arslan NC, Sokmen S, Avkan-Oguz V, Obuz F, Canda AE, Terzi C, Fuzun M (2017) Infectious complications after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. Surg Infect (Larchmt) 18(2):157–163. https://doi.org/10.1089/sur.2016.102

    Article  Google Scholar 

  7. Xiao H, Xiao Y, Quan H, Liu W, Pan S, Ouyang Y (2017) Intra-abdominal infection after radical gastrectomy for gastric cancer: Incidence, pathogens, risk factors and outcomes. Int J Surg 48:195–200. doi:https://doi.org/10.1016/j.ijsu.2017.07.081

    Article  PubMed  Google Scholar 

  8. Nespoli A, Gianotti L, Bovo G, Brivio F, Nespoli L, Totis M (2006) Impact of postoperative infections on survival in colon cancer patients. Surg Infect (Larchmt) 7(Suppl 2):S41–S43. doi:https://doi.org/10.1089/sur.2006.7.s2-41

    Article  Google Scholar 

  9. Tsujimoto H, Ichikura T, Ono S, Sugasawa H, Hiraki S, Sakamoto N, Yaguchi Y, Yoshida K, Matsumoto Y, Hase K (2009) Impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Ann Surg Oncol 16(2):311–318. doi:https://doi.org/10.1245/s10434-008-0249-8

    Article  PubMed  Google Scholar 

  10. Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M (2013) Poor survival rate in patients with postoperative intra-abdominal infectious complications following curative gastrectomy for gastric cancer. Ann Surg Oncol 20(5):1575–1583. doi:https://doi.org/10.1245/s10434-012-2720-9

    Article  PubMed  Google Scholar 

  11. Tan HJ, Hafez KS, Ye Z, Wei JT, Miller DC (2012) Postoperative complications and long-term survival among patients treated surgically for renal cell carcinoma. J Urol 187(1):60–66. doi:https://doi.org/10.1016/j.juro.2011.09.031

    Article  PubMed  Google Scholar 

  12. Kubota T, Hiki N, Sano T, Nomura S, Nunobe S, Kumagai K, Aikou S, Watanabe R, Kosuga T, Yamaguchi T (2014) Prognostic significance of complications after curative surgery for gastric cancer. Ann Surg Oncol 21(3):891–898. doi:https://doi.org/10.1245/s10434-013-3384-9

    Article  PubMed  Google Scholar 

  13. Hayashi T, Yoshikawa T, Aoyama T, Hasegawa S, Yamada T, Tsuchida K, Fujikawa H, Sato T, Ogata T, Cho H, Oshima T, Rino Y, Masuda M (2015) Impact of infectious complications on gastric cancer recurrence. Gastric Cancer 18(2):368–374. doi:https://doi.org/10.1007/s10120-014-0361-3

    Article  PubMed  Google Scholar 

  14. Andreou A, Biebl M, Dadras M, Struecker B, Sauer IM, Thuss-Patience PC, Chopra S, Fikatas P, Bahra M, Seehofer D, Pratschke J, Schmidt SC (2016) Anastomotic leak predicts diminished long-term survival after resection for gastric and esophageal cancer. Surgery 160(1):191–203. doi:https://doi.org/10.1016/j.surg.2016.02.020

    Article  PubMed  Google Scholar 

  15. Sierzega M, Kolodziejczyk P, Kulig J, Polish Gastric Cancer Study G (2010) Impact of anastomotic leakage on long-term survival after total gastrectomy for carcinoma of the stomach. Br J Surg 97(7):1035–1042. doi:https://doi.org/10.1002/bjs.7038

    Article  CAS  PubMed  Google Scholar 

  16. Yoo HM, Lee HH, Shim JH, Jeon HM, Park CH, Song KY (2011) Negative impact of leakage on survival of patients undergoing curative resection for advanced gastric cancer. J Surg Oncol 104(7):734–740. doi:https://doi.org/10.1002/jso.22045

    Article  PubMed  Google Scholar 

  17. Molteni M, Gemma S, Rossetti C (2016) The role of toll-like receptor 4 in infectious and noninfectious inflammation. Mediators Inflamm. https://doi.org/10.1155/2016/6978936

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hoebe K, Beutler B (2006) TRAF3: a new component of the TLR-signaling apparatus. Trends Mol Med 12(5):187–189. doi:https://doi.org/10.1016/j.molmed.2006.03.008

    Article  CAS  PubMed  Google Scholar 

  19. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301(5633):640–643. doi:https://doi.org/10.1126/science.1087262

    Article  CAS  PubMed  Google Scholar 

  20. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4(7):499–511. doi:https://doi.org/10.1038/nri1391

    Article  CAS  PubMed  Google Scholar 

  21. Deguine J, Barton GM (2014) MyD88: a central player in innate immune signaling. F1000Prime Rep 6:97. doi:https://doi.org/10.12703/P6-97

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kagan JC, Medzhitov R (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125(5):943–955. doi:https://doi.org/10.1016/j.cell.2006.03.047

    Article  CAS  PubMed  Google Scholar 

  23. Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300(5625):1524–1525. doi:https://doi.org/10.1126/science.1085536

    Article  CAS  PubMed  Google Scholar 

  24. Gowing SD, Chow SC, Cools-Lartigue JJ, Chen CB, Najmeh S, Jiang HY, Bourdeau F, Beauchamp A, Mancini U, Angers I, Giannias B, Spicer JD, Rousseau S, Qureshi ST, Ferri LE (2017) Gram-positive pneumonia augments non-small cell lung cancer metastasis via host toll-like receptor 2 activation. Int J Cancer 141(3):561–571. doi:https://doi.org/10.1002/ijc.30734

    Article  CAS  PubMed  Google Scholar 

  25. Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE (2011) LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res 71(5):1989–1998. doi:https://doi.org/10.1158/0008-5472.CAN-10-2833

    Article  CAS  PubMed  Google Scholar 

  26. Andrews EJ, Wang JH, Winter DC, Laug WE, Redmond HP (2001) Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression. J Surg Res 97(1):14–19. doi:https://doi.org/10.1006/jsre.2001.6090

    Article  CAS  PubMed  Google Scholar 

  27. Li J, Yin J, Shen W, Gao R, Liu Y, Chen Y, Li X, Liu C, Xiang R, Luo N (2017) TLR4 promotes breast cancer metastasis via Akt/GSK3beta/beta-catenin pathway upon LPS stimulation. Anat Rec (Hoboken) 300(7):1219–1229. https://doi.org/10.1002/ar.23590

    Article  CAS  Google Scholar 

  28. Horiguchi H, Tsujimoto H, Shinomiya N, Matsumoto Y, Sugasawa H, Yamori T, Miyazaki H, Saitoh D, Kishi Y, Ueno H (2020) A potential role of adhesion molecules on lung metastasis enhanced by local inflammation. Anticancer Res 40(11):6171–6178. https://doi.org/10.21873/anticanres.14637

    Article  CAS  PubMed  Google Scholar 

  29. Tanaka S, Saito Y, Kunisawa J, Kurashima Y, Wake T, Suzuki N, Shultz LD, Kiyono H, Ishikawa F (2012) Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rgammaKO mice. J Immunol 188(12):6145–6155. doi:https://doi.org/10.4049/jimmunol.1103660

    Article  CAS  PubMed  Google Scholar 

  30. Skirecki T, Kawiak J, Machaj E, Pojda Z, Wasilewska D, Czubak J, Hoser G (2015) Early severe impairment of hematopoietic stem and progenitor cells from the bone marrow caused by CLP sepsis and endotoxemia in a humanized mice model. Stem Cell Res Ther 6:142. doi:https://doi.org/10.1186/s13287-015-0135-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rodewohl A, Scholbach J, Leichsenring A, Koberle M, Lange F (2017) Age-dependent cellular reactions of the human immune system of humanized NOD scid gamma mice on LPS stimulus. Innate Immun 23(3):258–275. doi:https://doi.org/10.1177/1753425917690814

    Article  CAS  PubMed  Google Scholar 

  32. Klaver YL, Hendriks T, Lomme RM, Rutten HJ, Bleichrodt RP, de Hingh IH (2010) Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model. Br J Surg 97(12):1874–1880. doi:https://doi.org/10.1002/bjs.7249

    Article  CAS  PubMed  Google Scholar 

  33. Jacquet P, Sugarbaker PH (1996) Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res 82:359–374

    Article  CAS  PubMed  Google Scholar 

  34. Li W, Ng JM, Wong CC, Ng EKW, Yu J (2018) Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer. Oncogene 37(36):4903–4920. doi:https://doi.org/10.1038/s41388-018-0341-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hwang EH, Kim TH, Oh SM, Lee KB, Yang SJ, Park JH (2016) Toll/IL-1 domain-containing adaptor inducing IFN-beta (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation. Cytokine 77:127–134. doi:https://doi.org/10.1016/j.cyto.2015.11.010

    Article  CAS  PubMed  Google Scholar 

  36. Wang J, Feng X, Zeng Y, Fan J, Wu J, Li Z, Liu X, Huang R, Huang F, Yu X, Yang X (2013) Lipopolysaccharide (LPS)-induced autophagy is involved in the restriction of Escherichia coli in peritoneal mesothelial cells. BMC Microbiol 13:255. doi:https://doi.org/10.1186/1471-2180-13-255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Su B, Ceponis PJ, Lebel S, Huynh H, Sherman PM (2003) Helicobacter pylori activates Toll-like receptor 4 expression in gastrointestinal epithelial cells. Infect Immun 71(6):3496–3502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, Crowe S, Goldberg JB (2003) Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 278(35):32552–32560. doi:https://doi.org/10.1074/jbc.M305536200

    Article  CAS  PubMed  Google Scholar 

  39. Yokota S, Okabayashi T, Rehli M, Fujii N, Amano K (2010) Helicobacter pylori lipopolysaccharides upregulate toll-like receptor 4 expression and proliferation of gastric epithelial cells via the MEK1/2-ERK1/2 mitogen-activated protein kinase pathway. Infect Immun 78(1):468–476. doi:https://doi.org/10.1128/IAI.00903-09

    Article  CAS  PubMed  Google Scholar 

  40. Kawahara T, Teshima S, Oka A, Sugiyama T, Kishi K, Rokutan K (2001) Type I Helicobacter pylori lipopolysaccharide stimulates toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells. Infect Immun 69(7):4382–4389. doi:https://doi.org/10.1128/IAI.69.7.4382-4389.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wroblewski LE, Peek RM Jr, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23(4):713–739. doi:https://doi.org/10.1128/CMR.00011-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Isaza-Restrepo A, Martin-Saavedra JS, Velez-Leal JL, Vargas-Barato F, Riveros-Duenas R (2018) The peritoneum: beyond the tissue—a review. Front Physiol 9:738. https://doi.org/10.3389/fphys.2018.00738

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yung S, Chan TM (2012) Pathophysiological changes to the peritoneal membrane during PD-related peritonitis: the role of mesothelial cells. Mediators Inflamm. https://doi.org/10.1155/2012/484167

    Article  PubMed  PubMed Central  Google Scholar 

  44. Cui L, Johkura K, Liang Y, Teng R, Ogiwara N, Okouchi Y, Asanuma K, Sasaki K (2002) Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation. Cell Tissue Res 310(3):321–330. doi:https://doi.org/10.1007/s00441-002-0636-6

    Article  CAS  PubMed  Google Scholar 

  45. Chow SC, Gowing SD, Cools-Lartigue JJ, Chen CB, Berube J, Yoon HW, Chan CH, Rousseau MC, Bourdeau F, Giannias B, Roussel L, Qureshi ST, Rousseau S, Ferri LE (2015) Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation. Int J Cancer 136(6):1341–1350. doi:https://doi.org/10.1002/ijc.29111

    Article  CAS  PubMed  Google Scholar 

  46. Gowing SD, Chow SC, Cools-Lartigue JJ, Chen CB, Najmeh S, Goodwin-Wilson M, Jiang HY, Bourdeau F, Beauchamp A, Angers I, Giannias B, Spicer JD, Rousseau S, Qureshi ST, Ferri LE (2019) Gram-Negative pneumonia augments non-small cell lung cancer metastasis through host toll-like receptor 4 activation. J Thorac Oncol 14(12):2097–2108. https://doi.org/10.1016/j.jtho.2019.07.023

    Article  CAS  PubMed  Google Scholar 

  47. Yang Y, Qiu Y, Tang M, Wu Z, Hu W, Chen C (2017) Expression and function of transforming growth factorbetaactivated protein kinase 1 in gastric cancer. Mol Med Rep 16(3):3103–3110. doi:https://doi.org/10.3892/mmr.2017.6998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lai AZ, Cory S, Zhao H, Gigoux M, Monast A, Guiot MC, Huang S, Tofigh A, Thompson C, Naujokas M, Marcus VA, Bertos N, Sehat B, Perera RM, Bell ES, Page BD, Gunning PT, Ferri LE, Hallett M, Park M (2014) Dynamic reprogramming of signaling upon met inhibition reveals a mechanism of drug resistance in gastric cancer. Sci Signal 7(322):ra38. doi:https://doi.org/10.1126/scisignal.2004839

    Article  CAS  PubMed  Google Scholar 

  49. Burnett A, Lecompte MA, Trabulsi N, Dube P, Gervais MK, Trilling B, Cloutier AS, Sideris L (2019) Peritoneal carcinomatosis index predicts survival in colorectal patients undergoing HIPEC using oxaliplatin: a retrospective single-arm cohort study. World J Surg Oncol 17(1):83. doi:https://doi.org/10.1186/s12957-019-1618-4

    Article  PubMed  PubMed Central  Google Scholar 

  50. Elias D, Faron M, Iuga BS, Honore C, Dumont F, Bourgain JL, Dartigues P, Ducreux M, Goere D (2015) Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers. Ann Surg 261(1):157–163. doi:https://doi.org/10.1097/SLA.0000000000000582

    Article  PubMed  Google Scholar 

  51. Leiting JL, Grotz TE (2018) Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis. World J Gastrointest Oncol 10(10):282–289. doi:https://doi.org/10.4251/wjgo.v10.i10.282

    Article  PubMed  PubMed Central  Google Scholar 

  52. Chia CS, You B, Decullier E, Vaudoyer D, Lorimier G, Abboud K, Bereder JM, Arvieux C, Boschetti G, Glehen O, Group BR (2016) Patients with peritoneal carcinomatosis from gastric cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is cure a possibility? Ann Surg Oncol 23(6):1971–1979. https://doi.org/10.1245/s10434-015-5081-3

    Article  CAS  PubMed  Google Scholar 

  53. da Silva RG, Sugarbaker PH (2006) Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg 203(6):878–886. doi:https://doi.org/10.1016/j.jamcollsurg.2006.08.024

    Article  PubMed  Google Scholar 

  54. Chua TC, Saxena A, Schellekens JF, Liauw W, Yan TD, Fransi S, Zhao J, Morris DL (2010) Morbidity and mortality outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy at a single tertiary institution: towards a new perspective of this treatment. Ann Surg 251(1):101–106. doi:https://doi.org/10.1097/SLA.0b013e3181b5ae43

    Article  PubMed  Google Scholar 

  55. Mizumoto A, Canbay E, Hirano M, Takao N, Matsuda T, Ichinose M, Yonemura Y (2012) Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution in Japan. Gastroenterol Res Pract. https://doi.org/10.1155/2012/836425

    Article  PubMed  PubMed Central  Google Scholar 

  56. Liu JY, Yuan JP, Geng XF, Qu AP, Li Y (2015) Morphological study and comprehensive cellular constituents of milky spots in the human omentum. Int J Clin Exp Pathol 8(10):12877–12884

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Muccioli M, Benencia F (2014) Toll-like receptors in ovarian cancer as targets for immunotherapies. Front Immunol 5:341. https://doi.org/10.3389/fimmu.2014.00341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G (2006) TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res 66(7):3859–3868. doi:https://doi.org/10.1158/0008-5472.CAN-05-3948

    Article  CAS  PubMed  Google Scholar 

  59. Franchi L, Warner N, Viani K, Nunez G (2009) Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev 227(1):106–128. doi:https://doi.org/10.1111/j.1600-065X.2008.00734.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Correa P (2004) The biological model of gastric carcinogenesis. IARC Sci Publ 157:301–310

    Google Scholar 

  61. Matsuo K, Prather CP, Ahn EH, Eno ML, Tierney KE, Yessaian AA, Im DD, Rosenshein NB, Roman LD (2012) Significance of perioperative infection in survival of patients with ovarian cancer. Int J Gynecol Cancer 22(2):245–253. doi:https://doi.org/10.1097/IGC.0b013e31823bd6db

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Chantelle Janeiro for contribution to this study, the Immunophenotyping, Microscopy and Biobank Technology Platforms of the Research Institute of the McGill University Health Centre and staff for providing services and assistance with flow cytometry, imaging and tissue collection respectively. This study was funded by grants from the Canadian Institute of Health Research to L.F. and the Montreal General Hospital Foundation to S.D.B. and V.S. S.D.B. is supported by a Chercheur Boursier Junior 1 award from Les Fonds de Recherche du Québec-Santé (FRQ-S) and a Tomlinson Award from McGill University.

Author information

Authors and Affiliations

  1. Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada

    Veena Sangwan, Luai Al-Marzouki, Sanjima Pal, Vivian Stavrakos, Malak Alzahrani, Dorothy Antonatos, Yehonatan Nevo, Roni Rayes, France Bourdeau, Betty Giannias, Swneke Bailey, Jonathan Cools-Lartigue, Jonathan D. Spicer & Lorenzo Ferri

  2. Department of Pathology, McGill University, Montreal, Quebec, Canada

    Sophie Camilleri-Broët

  3. Department of Medicine, McGill University, Montreal, Quebec, Canada

    Simon Rousseau

  4. Research Institute – McGill University Health Centre, Montreal, Canada

    Veena Sangwan, Luai Al-Marzouki, Sanjima Pal, Vivian Stavrakos, Malak Alzahrani, Dorothy Antonatos, Yehonatan Nevo, Sophie Camilleri-Broët, Roni Rayes, France Bourdeau, Betty Giannias, Nicholas Bertos, Swneke Bailey, Simon Rousseau, Jonathan Cools-Lartigue, Jonathan D. Spicer & Lorenzo Ferri

  5. Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

    Malak Alzahrani

  6. Departments of Surgery and Oncology, Montreal General Hospital, McGill University, 1650 Cedar Avenue, Room L8-505, Montreal, Quebec, H3G 1A4, Canada

    Lorenzo Ferri

Authors
  1. Veena Sangwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luai Al-Marzouki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjima Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vivian Stavrakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Malak Alzahrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dorothy Antonatos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yehonatan Nevo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sophie Camilleri-Broët
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roni Rayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. France Bourdeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Betty Giannias
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nicholas Bertos
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Swneke Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Simon Rousseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jonathan Cools-Lartigue
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jonathan D. Spicer
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Lorenzo Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lorenzo Ferri.

Ethics declarations

Conflict of interest

The authors declare that they have conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sangwan, V., Al-Marzouki, L., Pal, S. et al. Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis. Clin Exp Metastasis 39, 323–333 (2022). https://doi.org/10.1007/s10585-021-10133-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-021-10133-8

Keywords

Search

Navigation