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PMID: 17466902 Published · ppublish English Journal Article Review

Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed?

The Lancet. Oncology ·Vol. 8 ·No. 5 ·2007-05-00 ·Pages 444-8

Bockhorn M, Jain RK, Munn LL

Abstract

Although millions of cells are shed from a tumour every day, haematogenous metastasis is believed to be very inefficient. This inefficiency is widely assumed to be a result of the destruction of cells in the bloodstream by shear stress and the immune system and a slow rate of extravasation and proliferation in the stroma at a secondary site. Here, we propose that, whereas active intravasation of cells into the circulation is important in some tumours, others might shed cells passively into the blood or lymphatic vessels without the involvement of active cell migration. We discuss the evidence for and against this passive-shedding hypothesis and the implications for future treatments.

MeSH Terms
Blood Vessels/pathology Cell Adhesion Humans Neoplasm Invasiveness/pathology Neoplasm Metastasis/pathology Neoplasms/blood supply,pathology Neovascularization, Pathologic
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bockhorn Maximilian
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany.
Jain Rakesh K
Munn Lance L
References (61)
61 references, click to expand
  1. Epigenetic silencing of maspin gene expression in human breast cancers.
    Int J Cancer. 2000 Mar 15;85(6):805-10 PMID: 10709100
  2. A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis.
    Biomed Microdevices. 2006 Jun;8(2):109-18 PMID: 16688570
  3. Clinical targets for anti-metastasis therapy.
    Adv Cancer Res. 2000;79:91-121 PMID: 10818678
  4. Imaging of cancer invasion and metastasis using green fluorescent protein.
    Eur J Cancer. 2000 Aug;36(13 Spec No):1671-80 PMID: 10959053
  5. Angiogenesis in cancer and other diseases.
    Nature. 2000 Sep 14;407(6801):249-57 PMID: 11001068
  6. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14608-13 PMID: 11121063
  7. Circulating breast cancer cells are frequently apoptotic.
    Am J Pathol. 2001 Jul;159(1):17-20 PMID: 11438448
  8. Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough.
    Biochim Biophys Acta. 2001 Nov 30;1552(1):39-45 PMID: 11781114
  9. The seed and soil hypothesis: vascularisation and brain metastases.
    Lancet Oncol. 2002 Jan;3(1):53-7 PMID: 11905606
  10. Solid stress facilitates spheroid formation: potential involvement of hyaluronan.
    Br J Cancer. 2002 Mar 18;86(6):947-53 PMID: 11953828
  11. New functions for the matrix metalloproteinases in cancer progression.
    Nat Rev Cancer. 2002 Mar;2(3):161-74 PMID: 11990853
  12. Critical determinants of metastasis.
    Semin Cancer Biol. 2002 Apr;12(2):89-96 PMID: 12027580
  13. A progression puzzle.
    Nature. 2002 Aug 22;418(6900):823 PMID: 12192390
  14. Intravascular location of breast cancer cells after spontaneous metastasis to the lung.
    Am J Pathol. 2002 Sep;161(3):749-53 PMID: 12213701
  15. A molecular signature of metastasis in primary solid tumors.
    Nat Genet. 2003 Jan;33(1):49-54 PMID: 12469122
  16. Role of integrins in cell invasion and migration.
    Nat Rev Cancer. 2002 Feb;2(2):91-100 PMID: 12635172
  17. Molecular regulation of vessel maturation.
    Nat Med. 2003 Jun;9(6):685-93 PMID: 12778167
  18. Matrix metalloproteinases and tumor progression.
    Adv Exp Med Biol. 2003;532:91-107 PMID: 12908552
  19. Allelic diversity in the host genetic background may be an important determinant in tumor metastatic dissemination.
    Cancer Lett. 2003 Oct 28;200(2):97-105 PMID: 14568162
  20. Applying the principles of stem-cell biology to cancer.
    Nat Rev Cancer. 2003 Dec;3(12):895-902 PMID: 14737120
  21. Pathology: cancer cells compress intratumour vessels.
    Nature. 2004 Feb 19;427(6976):695 PMID: 14973470
  22. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters.
    Lancet Oncol. 2004 Apr;5(4):254-8 PMID: 15050959
  23. Differential gene expression in metastasizing cells shed from kidney tumors.
    Cancer Res. 2004 Apr 1;64(7):2469-73 PMID: 15059900
  24. Stromal cell-derived factor-1alpha promotes melanoma cell invasion across basement membranes involving stimulation of membrane-type 1 matrix metalloproteinase and Rho GTPase activities.
    Cancer Res. 2004 Apr 1;64(7):2534-43 PMID: 15059909
  25. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors.
    Cancer Res. 2004 Jun 1;64(11):3731-6 PMID: 15172975
  26. Cancer stem cells persist in many cancer cell lines.
    Cell Cycle. 2004 Apr;3(4):414-5 PMID: 15004528
  27. Differential effects of EGF gradient profiles on MDA-MB-231 breast cancer cell chemotaxis.
    Exp Cell Res. 2004 Oct 15;300(1):180-9 PMID: 15383325
  28. Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles.
    Oncogene. 2004 Sep 23;23(44):7366-77 PMID: 15326482
  29. Microenvironmental and cellular consequences of altered blood flow in tumours.
    Br J Radiol. 2003;76 Spec No 1:S11-22 PMID: 15456710
  30. Apoptosis of circulating tumor cells in prostate cancer patients.
    Cytometry A. 2004 Nov;62(1):46-53 PMID: 15472900
  31. The relationship of embolic homogeneity, number, size and viability to the incidence of experimental metastasis.
    Eur J Cancer. 1973 Mar;9(3):223-7 PMID: 4787857
  32. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation.
    Cancer Res. 1974 May;34(5):997-1004 PMID: 4841969
  33. Quantitation of cell shedding into efferent blood of mammary adenocarcinoma.
    Cancer Res. 1975 Mar;35(3):512-6 PMID: 1090362
  34. The significance of hematogenous tumor cell clumps in the metastatic process.
    Cancer Res. 1976 Mar;36(3):889-94 PMID: 1253177
  35. Cancer cell traffic from the lungs to the liver: an example of metastatic inefficiency.
    Int J Cancer. 1980 Mar 15;25(3):385-92 PMID: 7390660
  36. 'Seed and soil' revisited: mechanisms of site-specific metastasis.
    Cancer Metastasis Rev. 1982;1(1):5-16 PMID: 6764375
  37. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.
    N Engl J Med. 1986 Dec 25;315(26):1650-9 PMID: 3537791
  38. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice.
    Cancer Res. 1988 Dec 1;48(23):6863-71 PMID: 2846163
  39. Desmoplasia and its relevance to colorectal tumour invasion.
    Int J Cancer. 1993 Jan 2;53(1):62-9 PMID: 7677932
  40. Metastatic inefficiency: the scientific basis for resection of liver metastases from colorectal cancer.
    J Surg Oncol Suppl. 1993;3:158-60 PMID: 8503973
  41. Adhesion molecules in tumor metastasis.
    Semin Cancer Biol. 1993 Aug;4(4):219-29 PMID: 8400144
  42. Cell adhesion and tumor metastasis.
    Princess Takamatsu Symp. 1994;24:99-105 PMID: 8983067
  43. The regulation of neovascularization of matrix metalloproteinases and their inhibitors.
    Stem Cells. 1997;15(3):180-9 PMID: 9170209
  44. Early events of metastasis in the microcirculation involve changes in gene expression of cancer cells. Tracking mRNA levels of metastasizing cancer cells in the chick embryo chorioallantoic membrane.
    Am J Pathol. 1997 Jun;150(6):2099-112 PMID: 9176401
  45. Apoptosis in metastatic cancer cells.
    Crit Rev Oncol Hematol. 1997 Apr;25(3):175-86 PMID: 9177940
  46. Solid stress inhibits the growth of multicellular tumor spheroids.
    Nat Biotechnol. 1997 Aug;15(8):778-83 PMID: 9255794
  47. Detection and characterization of carcinoma cells in the blood.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4589-94 PMID: 9539782
  48. Tumor induction of VEGF promoter activity in stromal cells.
    Cell. 1998 Sep 18;94(6):715-25 PMID: 9753319
  49. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy.
    Science. 2005 Jan 7;307(5706):58-62 PMID: 15637262
  50. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis.
    Nat Rev Cancer. 2005 Oct;5(10):786-95 PMID: 16175178
  51. Mechanisms of gradient sensing and chemotaxis: conserved pathways, diverse regulation.
    Cell Cycle. 2006 Jun;5(11):1130-4 PMID: 16760661
  52. Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma.
    Oncogene. 2006 Jul 20;25(31):4257-66 PMID: 16518413
  53. Loss of proline-rich tyrosine kinase 2 function induces spreading and motility of epithelial prostate cells.
    J Cell Physiol. 2006 Oct;209(1):74-80 PMID: 16783820
  54. Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential.
    Int J Cancer. 2006 Dec 1;119(11):2567-74 PMID: 16988946
  55. Epigenetic stem cell signature in cancer.
    Nat Genet. 2007 Feb;39(2):157-8 PMID: 17200673
  56. Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model.
    Cancer Res. 2007 Mar 15;67(6):2729-35 PMID: 17363594
  57. Cells shed from tumours show reduced clonogenicity, resistance to apoptosis, and in vivo tumorigenicity.
    Br J Cancer. 1999 Nov;81(5):756-9 PMID: 10555742
  58. Modern pathology: prognostic parameters in squamous cell carcinoma of the esophagus.
    Recent Results Cancer Res. 2000;155:15-27 PMID: 10693235
  59. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
    Cell. 2006 Jan 27;124(2):263-6 PMID: 16439202
  60. Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment.
    Cell Mol Life Sci. 2006 Feb;63(4):449-68 PMID: 16416030
  61. Openings between defective endothelial cells explain tumor vessel leakiness.
    Am J Pathol. 2000 Apr;156(4):1363-80 PMID: 10751361
Article Info
Journal
The Lancet. Oncology
Abbr.
Lancet Oncol
ISSN
1470-2045
DOI
10.1016/S1470-2045(07)70140-7
Published
2007-05-00
Pages
444-8
Language
English
Region
England
NLM ID
100957246
PMCID
PMC2712886
Subset
IM
Grants
NHLBI NIH HHS · R01 HL064240 · United States
NHLBI NIH HHS · R01 HL064240-08 · United States
External Links
PubMed source DOI: 10.1016/S1470-2045(07)70140-7 PMC Full Text View journal details
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