Skip to main content

Advertisement

SpringerLink
Log in

Cancer Cells Cause Vascular Endothelial Cell (vEC) Retraction via 12(S)HETE Secretion; The Possible Role of Cancer Cell Derived Microparticle

  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cancer cell mediated vascular endothelial cell (vEC) retraction plays a pivotal role in cancer metastasis. The aim of this study is to clarify the biochemical character of vEC retraction factor derived from human breast cancer cell line, MCF-7.

Methods and Results

In order to estimate vEC retracting activity, transwell chamber assay system was employed. We first tested the effects of trypsin digestion as well as lipid extraction of culture medium (CM). Trypsin digestion of CM resulted in approximately 40% loss of vEC retracting activity and lipid extraction of CM by Brigh and Dyer methods recovered approximately 60% of vEC retracting activity, suggesting that approximately 60% of vEC retracting activity in MCF-7 derived CM is due to lipid. Although Nordihydroguaiaretic acid (NDGA), the specific lipoxygenase inhibitor, suppressed vEC retracting activity in CM, Acetyl salicylic acid (ASA), a specific cyclooxygenase inhibitor, did not affect the activity, suggesting that lipid exerting vEC retracting activity in CM belongs to lipoxygenase mediated arachidonate metabolites. Thin layer chromatography clearly demonstrated that Rf value of lipid vEC retracting factor in CM is identical to 12HETE. Authentic 12(S)HETE, but not 12(R)HETE, showed vEC retracting activity. After the ultracentrifugation of CM, most lipid vEC retracting activity was recovered from the pellet fraction, and flow cytometric analysis using specific antibody against 12(S)HETE clearly showed the association of 12(S)HETE with small particle in CM.

Conclusion

These findings suggested the principal involvement of 12(S)HETE in cancer cell derived microparticles in cancer cell mediated vEC retraction.

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.
FIG. 6.
FIG. 7.
FIG. 8.
FIG. 9.

Similar content being viewed by others

References

  1. Fidler IJ, Gerstein DM, Hart IR. The biology of cancer invasion and metastasis.Advanc Cancer Res 1978; 28:149–250

    Article  CAS  Google Scholar 

  2. Nicolson GL. Organ colonization and the cell-surface properties of malignant cells. Biochem biophys Acta 1982; 695:113–76

    PubMed  CAS  Google Scholar 

  3. Carr I, McGinty F, Norris P. The fine structure of neoplastic invasion:invasion of liver,skeletal muscle and lymphatic vessels by the Rd/3 tumour. J pathol 1976; 118:91–99

    Article  PubMed  CAS  Google Scholar 

  4. Akedo H, Shinkai K, Mukai M, et al. Interaction of rat ascites hepatoma cells with cultured mesothelial cell layers:a model for tumor invasion. Cancer Res 1986; 46:2416–22

    PubMed  CAS  Google Scholar 

  5. Ohigashi H, Shinkai K, Mukai M, et al. In vitro invasion of endothelial cell monolayer by rat ascites hepatoma cells. Jpn J Cancer Res 1989; 80:818–21

    PubMed  CAS  Google Scholar 

  6. Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol Aug 1993; 4(4):219–29

    CAS  Google Scholar 

  7. Nakamori S, Okamoto H, et.al. Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells. Ann Surg Oncol 1997; 4:361–368

    Article  PubMed  CAS  Google Scholar 

  8. Shibuya M. Angiogenesis–vascular endothelial growth factor and its receptors. Hum Cell 1999; 12(1):17–24

    PubMed  CAS  Google Scholar 

  9. David M, Humphrey Linda M, McManus, Kiyoshi Satoguchi, et al. Vasoactive Properties of Acetyl Glyceryl Ether Phosphorylcholine and Analogues. Lab Invest 1982; 42:422–427

  10. Kusama T, Nakamori S, et al. Enhancement of in vitro tumor-cell transcellular migration by tumor-cell-secreted endothelial-cell-retraction factor. Int J Cancer 1995; 63:112–118

    Article  PubMed  CAS  Google Scholar 

  11. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Bioch Physiol 1959; 37:911–917

    CAS  Google Scholar 

  12. Okuma M, Uchino H. Altered arachidonate metabolism by platelets in patients with myeloproliferative disorders. Blood 1979; 54(6):1258–71

    PubMed  CAS  Google Scholar 

  13. Yamamoto T, Nagano H, Sakon M, et al. Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma. Clin Cancer Res 2004; 10(23):7884–95

    Article  PubMed  CAS  Google Scholar 

  14. Majno G, Palade GE. Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol 1961; 11:571–605

    Article  PubMed  CAS  Google Scholar 

  15. Dahlen SE, Jakob Bjork, Per Hedqvist, et al. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules. Proc Natl Acad Sci 1988; 78:3887–3891

  16. Rabiet MJ, Plantier JL, Rival Y, et al. Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler Thromb Vasc Biol 1996; 16(3):488–96

    PubMed  CAS  Google Scholar 

  17. Burke-Gaffney A, Keenan AK. Modulation of human endothelial cell permeability by combinations of the cytokines interleukin-1 alpha/beta, tumor necrosis factor-alpha and interferon-gamma. Immunopharmacology 1993; 25(1):1–9

    Article  PubMed  CAS  Google Scholar 

  18. Maruo N, Morita I, Shirao M, et al. IL-6 increases endothelial permeability in vitro. Endocrinology 1992; 131(2):710–4

    Article  PubMed  CAS  Google Scholar 

  19. Schraufstatter IU, Chung J, Burger M. IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways. Am J Physiol Lung Cell Mol Physiol 2001; 280(6):1094–1103

    Google Scholar 

  20. Horvath CJ, Ferro J, Thomas, Jesmok Gary, et al. Recombinant tumor necrosis factor increase pulmonary vascular permeability independent of neutrophils. Proc Natil Acad Sci 1988; 85:9219–9223

  21. Kenneth V, Honn Dean G, Tang, et al. Tumo cell-derived 12(S)-hydroxyeicosatetraenoic acid induces microvascular endothelial cell retraction. Cancer Research 1994; 54:565–574

  22. Kenneth V, Honn Irma M, Grossi, et al. Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)-HETE-induced endothelial cell retraction. The FASEB J 1989; 2285–2293

  23. Iwamoto S, Kawasaki T, Kambayashi J, et al. Platelet Microparticles: A carrier of Platelet-Activating Factor? Biochem Biophys Res Commun 1996; 218(3):940–944

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suitacity, Osaka, Japan

    Keiji Uchide MD, Masato Sakon MD, Hideo Ariyoshi MD, Syouji Nakamori MD, Masaru Tokunaga MD & Morito Monden MD

Authors
  1. Keiji Uchide MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masato Sakon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideo Ariyoshi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Syouji Nakamori MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masaru Tokunaga MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Morito Monden MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keiji Uchide MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Uchide, K., Sakon, M., Ariyoshi, H. et al. Cancer Cells Cause Vascular Endothelial Cell (vEC) Retraction via 12(S)HETE Secretion; The Possible Role of Cancer Cell Derived Microparticle. Ann Surg Oncol 14, 862–868 (2007). https://doi.org/10.1245/s10434-006-9225-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-006-9225-3

Keywords

Search

Navigation