Skip to main content

Advertisement

Log in

Hydroxyethyl starch 200/0.5 decreases circulating tumor cells of colorectal cancer patients and reduces metastatic potential of colon cancer cell line through inhibiting platelets activation

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Platelets play an important role in metastasis of circulating tumor cells (CTCs). It has been demonstrated that hydroxyethyl starch (HES) inhibits platelets function. However, the effect of HES on CTCs in patients with colorectal cancer remains unclear. We compared the effects of HES 200/0.5 and HES 130/0.4 on CTCs and platelets activation of colorectal patients in this study. Additionally, the effects of HES 200/0.5 or HES 130/0.4 on metastasis ability of colon cancer cell line that stimulated by activated platelets have been explored. In vivo, 90 patients undergoing colorectal cancer radical surgery received randomly 15 mL/kg of HES 200/0.5 (n = 45) or HES 130/0.4 (n = 45) infusion before surgery. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa), CD62P and platelets aggregation rate (PAR) were evaluated pre-, intra- and postoperatively. Cytokeratin-20 (CK-20) mRNA was detected by reverse transcriptase polymerase chain reaction before and after surgery. In vitro, colon cancer SW480 cells were incubated with activated platelets in the presence or absence HES 200/0.5 or HES 130/0.4. The metastasis ability of SW480 cells was assessed by Transwell assay. The results showed that CK-20 mRNA positive rate in HES 200/0.5 group after surgery was decreased significantly as compared to group HES 130/0.4 (χ 2 = 6.164, P = 0.013). Simultaneously, a more pronounced inhibition of platelets activation was observed in group HES 200/0.5. A positive correlation between platelets activation marker and CK-20 mRNA positive rate was found. In vitro, HES 200/0.5, but not HES 130/0.4, decreased the invasion and migration ability of SW480 cells that induced by activated platelets. Besides, the expression of GPIIb/IIIa, CD62P and PAR was inhibited more strongly in group HES 200/0.5 than those in group HES 130/0.4. In summary, we found that HES 200/0.5 significantly decreased CTCs of patients undergoing colorectal cancer radical surgery as compared to HES 130/0.4, which might be associated with inhibiting platelets activation of HES 200/0.5. Furthermore, HES 200/0.5, but not HES 130/0.4, reduced the metastatic potential of colon cell line stimulated by activated platelets through depressing platelets activation. Modulation of platelets activity may be a novel strategy to minimize the risk of metastasis during surgery.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics for hispanics/latinos, 2012. CA Cancer J Clin. 2012;62:283–98.

    Article  PubMed  Google Scholar 

  2. Sample CB, Watson M, Okrainec A, et al. Long-term outcomes of laparoscopic surgery for colorectal cancer. Surg Endosc. 2006;20:30–4.

    Article  CAS  PubMed  Google Scholar 

  3. Li C, Cai S, Wang X, Jiang Z. Hypomethylation-associated up-regulation of TCF3 expression and recurrence in stage II and III colorectal cancer. PLoS One. 2014;9:e112005.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Zhang W, Song T. The progress in adjuvant therapy after curative resection of liver metastasis from colorectal cancer. Drug Discov Ther. 2014;8:194–200.

    Article  PubMed  Google Scholar 

  5. Neeman E, Ben-Eliyahu S. Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun. 2013;30(Suppl):S32–40.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Exadaktylos AK, Buggy DJ, Moriarty DC, et al. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660–4.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer. 2009;9:302–12.

    Article  CAS  PubMed  Google Scholar 

  8. Goldfarb Y, Sorski L, Benish M, et al. Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses. Ann Surg. 2011;253:798–810.

    Article  PubMed  Google Scholar 

  9. Benish M, Bartal I, Goldfarb Y, et al. Perioperative use of beta-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol. 2008;15:2042–52.

    Article  PubMed  Google Scholar 

  10. Kin C, Kidess E, Poultsides GA, et al. Colorectal cancer diagnostics: biomarkers, cell-free DNA, circulating tumor cells and defining heterogeneous populations by single-cell analysis. E Expert Rev Mol Diagn. 2013;13:581–99.

    Article  CAS  Google Scholar 

  11. Kuboki Y, Matsusaka S, Minowa S, et al. Circulating tumor cell (CTC) count and epithelial growth factor receptor expression on CTCs as biomarkers for cetuximab efficacy in advanced colorectal cancer. Anticancer Res. 2013;33:3905–10.

    CAS  PubMed  Google Scholar 

  12. Peach G, Kim C, Zacharakis E, et al. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer. 2010;102:1327–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Groot Koerkamp B, Rahbari NN, Buchler MW, et al. Circulating tumor cells and prognosis of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer: a meta-analysis. Ann Surg Oncol. 2013;20:2156–65.

    Article  PubMed  Google Scholar 

  14. Lagoudianakis EE, Kataki A, Manouras A, et al. Detection of epithelial cells by RT-PCR targeting CEA, CK20, and TEM-8 in colorectal carcinoma patients using OncoQuick density gradient centrifugation system. J Surg Res. 2009;155:183–90.

    Article  CAS  PubMed  Google Scholar 

  15. Palumbo JS. Mechanisms linking tumor cell-associated procoagulant function to tumor dissemination. Semin Thromb Hemost. 2008;34:154–60.

    Article  CAS  PubMed  Google Scholar 

  16. Thorson CM, Van Haren RM, Ryan ML, et al. Pre-existing hypercoagulability in patients undergoing potentially curative cancer resection. Surgery. 2014;155:134–44.

    Article  PubMed  Google Scholar 

  17. Juttner B, Kuse ER, Elsner HA, et al. Differential platelet receptor expression following hydroxyethyl starch infusion in thrombocytopaenic orthotopic liver transplantation recipients. Eur J Anaesthesiol. 2004;21:309–13.

    Article  CAS  PubMed  Google Scholar 

  18. Westphal M, James MF, Kozek-Langenecker S, et al. Hydroxyethyl starches: different products–different effects. Anesthesiology. 2009;111:187–202.

    Article  CAS  PubMed  Google Scholar 

  19. Liang H, Yang CX, Li H, et al. The effects of preloading infusion with hydroxyethyl starch 200/0.5 or 130/0.4 solution on hypercoagulability and excessive platelet activation of patients with colon cancer. Blood Coagul Fibrinolysis. 2010;21:406–13.

    Article  CAS  PubMed  Google Scholar 

  20. Wittlinger M, Schlapfer M, De Conno E, et al. The effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells. Anesth Analg. 2010;110:531–40.

    Article  CAS  PubMed  Google Scholar 

  21. Thyes C, Madjdpour C, Frascarolo P, et al. Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs. Anesthesiology. 2006;105:1228–37.

    Article  CAS  PubMed  Google Scholar 

  22. Li Q, Cai G, Li D, et al. Better long-term survival in young patients with non-metastatic colorectal cancer after surgery, an analysis of 69,835 patients in SEER database. PLoS One. 2014;9:e93756.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Hofman V, Ilie MI, Long E, et al. Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the cell search assay and the isolation by size of epithelial tumor cell method. Int J Cancer. 2011;129:1651–60.

    Article  CAS  PubMed  Google Scholar 

  24. Ren C, He P, Zhang J, et al. Malignant characteristics of circulating tumor cells and corresponding primary tumor in a patient with esophageal squamous cell carcinoma before and after surgery. Cancer Biol Ther. 2011;11:633–8.

    Article  PubMed  Google Scholar 

  25. Pesta M, Fichtl J, Kulda V, et al. Monitoring of circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. Anticancer Res. 2013;33:2239–43.

    CAS  PubMed  Google Scholar 

  26. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11:123–34.

    Article  CAS  PubMed  Google Scholar 

  27. Steinert G, Scholch S, Niemietz T, et al. Immune escape and survival mechanisms in circulating tumor cells of colorectal cancer. Cancer Res. 2014;74:1694–704.

    Article  CAS  PubMed  Google Scholar 

  28. Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904.

    Article  CAS  PubMed  Google Scholar 

  29. Ware J. Fragmenting the platelet to reduce metastasis. Blood. 2012;120:2779–80.

    Article  CAS  PubMed  Google Scholar 

  30. Jurasz P, Alonso-Escolano D, Radomski MW. Platelet–cancer interactions: mechanisms and pharmacology of tumour cell-induced platelet aggregation. Br J Pharmacol. 2004;143:819–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Borsig L. The role of platelet activation in tumor metastasis. Expert Rev Anticancer Ther. 2008;8:1247–55.

    Article  CAS  PubMed  Google Scholar 

  32. Schneider GS, Rockman CB, Berger JS. Platelet activation increases in patients undergoing vascular surgery. Thromb Res. 2014;134:952–6.

    Article  CAS  PubMed  Google Scholar 

  33. Kedzierska M, Czernek U, Szydlowska-Pazera K, et al. The changes of blood platelet activation in breast cancer patients before surgery, after surgery, and in various phases of the chemotherapy. Platelets. 2013;24:462–8.

    Article  CAS  PubMed  Google Scholar 

  34. Hundt S, Haug U, Brenner H. Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev. 2007;16:1935–53.

    Article  CAS  PubMed  Google Scholar 

  35. Guller U, Zajac P, Schnider A, et al. Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer. Ann Surg. 2002;236:768–75.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Retz M, Lehmann J, Roder C, et al. Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for the detection of circulating tumor cells in peripheral blood and bone marrow of bladder cancer patients. Eur Urol. 2001;39:507–15.

    Article  CAS  PubMed  Google Scholar 

  37. Katsumata K, Sumi T, Mori Y, et al. Detection and evaluation of epithelial cells in the blood of colon cancer patients using RT-PCR. Int J Clin Oncol. 2006;11:385–9.

    Article  PubMed  Google Scholar 

  38. Sato N, Hayashi N, Imamura Y, et al. Usefulness of transcription-reverse transcription concerted reaction method for detecting circulating tumor cells in patients with colorectal cancer. Ann Surg Oncol. 2012;19:2060–5.

    Article  PubMed  Google Scholar 

  39. Romiti A, Raffa S, Di Rocco R, et al. Circulating tumor cells count predicts survival in colorectal cancer patients. J Gastrointestin Liver Dis. 2014;23:279–84.

    PubMed  Google Scholar 

  40. Welinder C, Jansson B, Lindell G, et al. Cytokeratin 20 improves the detection of circulating tumor cells in patients with colorectal cancer. Cancer Lett. 2015;358:43–6.

    Article  CAS  PubMed  Google Scholar 

  41. Stegner D, Dutting S, Nieswandt B. Mechanistic explanation for platelet contribution to cancer metastasis. Thromb Res. 2014;133(Suppl 2):S149–57.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Foshan Science and Technology Bureau Project for Medicine Investigation (2014AB00290).

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hua Liang or Bin Zhang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, H., Yang, C., Zhang, B. et al. Hydroxyethyl starch 200/0.5 decreases circulating tumor cells of colorectal cancer patients and reduces metastatic potential of colon cancer cell line through inhibiting platelets activation. Med Oncol 32, 151 (2015). https://doi.org/10.1007/s12032-015-0601-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0601-3

Keyword

Navigation