Home LiteratureArticle Details
PMID: 21522121 Published · ppublish English Journal Article Review

Clinical implications of cancer self-seeding.

Nature reviews. Clinical oncology ·Vol. 8 ·No. 6 ·2011-06-00 ·Pages 369-77

Comen E, Norton L, Massagué J

Abstract

Most metastatic cancers are incurable--a fact that underscores the limitations of our existing paradigms for understanding metastasis. In this Review, we use breast cancer to explore many of the enigmas revealed by these existing paradigms. Traditionally, metastatic models describe metastasis as a unidirectional process, whereby cancer cells leave a primary tumor and unidirectionally seed metastasis in regional lymph nodes or distant sites. By contrast, recent data indicate that metastasis is a multidirectional process whereby cancer cells can seed distant sites as well as the primary tumor itself. This later process, known as 'self-seeding,' has been validated in diverse experimental models. Here, we show that the self-seeding model may answer many of the mysteries inherent to cancer metastasis. Indeed, reframing our understanding of metastasis within the self-seeding model offers new opportunities for prevention and cure of metastatic cancer.

MeSH Terms
Animals Breast Neoplasms/secondary Disease Progression Female Humans Neoplasm Seeding Neoplastic Cells, Circulating/pathology
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Comen Elizabeth
Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Weill College of Medicine of Cornell University, New York, NY 10021, USA.
Norton Larry
Massagué Joan
References (62)
62 references, click to expand
  1. Age-related lobular involution and risk of breast cancer.
    J Natl Cancer Inst. 2006 Nov 15;98(22):1600-7 PMID: 17105983
  2. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial.
    J Natl Cancer Inst. 2008 Jan 16;100(2):121-33 PMID: 18182617
  3. A Gompertzian model of human breast cancer growth.
    Cancer Res. 1988 Dec 15;48(24 Pt 1):7067-71 PMID: 3191483
  4. Tumor-to-tumor metastasis: report of a case of renal cell carcinoma metastasizing to a pancreatic endocrine neoplasm.
    J Clin Oncol. 2011 Apr 10;29(11):e303-4 PMID: 21245422
  5. Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy.
    Oncologist. 2005 Jun-Jul;10(6):370-81 PMID: 15967831
  6. Survival outcomes in node-negative breast cancer patients evaluated with complete axillary node dissection versus sentinel lymph node biopsy.
    Ann Surg Oncol. 2006 May;13(5):708-11 PMID: 16538416
  7. Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer.
    Nat Rev Cancer. 2008 Apr;8(4):309-16 PMID: 18337733
  8. I. The Results of Radical Operations for the Cure of Carcinoma of the Breast.
    Ann Surg. 1907 Jul;46(1):1-19 PMID: 17861990
  9. Lung metastasis genes couple breast tumor size and metastatic spread.
    Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6740-5 PMID: 17420468
  10. The epithelial-mesenchymal transition generates cells with properties of stem cells.
    Cell. 2008 May 16;133(4):704-15 PMID: 18485877
  11. A role for chemotherapy as an adjunct to surgery.
    Cancer Res. 1957 Dec;17(11):1098-101 PMID: 13489715
  12. Deciphering death: a commentary on Gompertz (1825) 'On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies'.
    Philos Trans R Soc Lond B Biol Sci. 2015 Apr 19;370(1666): PMID: 25750242
  13. Hallmarks of cancer: the next generation.
    Cell. 2011 Mar 4;144(5):646-74 PMID: 21376230
  14. Tumor vasculature address book: identification of stage-specific tumor vessel zip codes by phage display.
    Cancer Cell. 2003 Nov;4(5):331-3 PMID: 14667498
  15. Survival differences among women with de novo stage IV and relapsed breast cancer.
    Ann Oncol. 2010 Nov;21(11):2169-2174 PMID: 20427349
  16. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.
    JAMA. 2011 Feb 9;305(6):569-75 PMID: 21304082
  17. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.
    J Clin Oncol. 2003 Apr 15;21(8):1431-9 PMID: 12668651
  18. The prognostic implications of circulating tumor cells in patients with breast cancer.
    Cancer Invest. 2008 Mar;26(2):109-14 PMID: 18259939
  19. Latent bone metastasis in breast cancer tied to Src-dependent survival signals.
    Cancer Cell. 2009 Jul 7;16(1):67-78 PMID: 19573813
  20. Breast cancer chemotherapy.
    Cancer J. 2007 May-Jun;13(3):141-7 PMID: 17620762
  21. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.
    N Engl J Med. 1996 May 23;334(21):1356-61 PMID: 8614420
  22. Tumor self-seeding by circulating cancer cells.
    Cell. 2009 Dec 24;139(7):1315-26 PMID: 20064377
  23. Cancer stem cells, self-seeding, and decremented exponential growth: theoretical and clinical implications.
    Breast Dis. 2008;29:27-36 PMID: 19029622
  24. Gene expression profiling of breast cancer: a new tumor marker.
    J Clin Oncol. 2005 Mar 10;23(8):1631-5 PMID: 15755970
  25. Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy.
    Cancer Res. 2004 Dec 1;64(23):8558-65 PMID: 15574762
  26. Mammary involution and breast cancer risk: transgenic models and clinical studies.
    J Mammary Gland Biol Neoplasia. 2009 Jun;14(2):181-91 PMID: 19404726
  27. Tumor size, sensitivity to therapy, and design of treatment schedules.
    Cancer Treat Rep. 1977 Oct;61(7):1307-17 PMID: 589597
  28. Mammographic density is related to stroma and stromal proteoglycan expression.
    Breast Cancer Res. 2003;5(5):R129-35 PMID: 12927043
  29. Results of treating 1,178 patients with breast cancer by radical mastectomy and postoperative irradiation where metastases to axillary lymph nodes occurred.
    J Surg Oncol. 1979;12(2):137-53 PMID: 491682
  30. Karnofsky Memorial Lecture. Natural history of small breast cancers.
    J Clin Oncol. 1994 Oct;12(10):2229-34 PMID: 7931493
  31. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion.
    Genes Dev. 2010 Feb 1;24(3):241-55 PMID: 20080943
  32. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.
    Lancet. 2005 Dec 17;366(9503):2087-106 PMID: 16360786
  33. Of microenvironments and mammary stem cells.
    Stem Cell Rev. 2007 Jun;3(2):137-46 PMID: 17873346
  34. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery.
    Cancer. 1985 Sep 1;56(5):979-90 PMID: 2990668
  35. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
    Curr Opin Immunol. 2006 Apr;18(2):206-13 PMID: 16464564
  36. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer.
    J Clin Oncol. 2005 Oct 20;23(30):7703-20 PMID: 16157938
  37. The molecular pathology of breast cancer progression.
    J Pathol. 2011 Jan;223(2):307-17 PMID: 21125683
  38. Local therapy and survival in breast cancer.
    N Engl J Med. 2007 Jun 7;356(23):2399-405 PMID: 17554121
  39. Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study.
    Anal Cell Pathol (Amst). 2010;33(3):165-73 PMID: 20978320
  40. Metastasis: from dissemination to organ-specific colonization.
    Nat Rev Cancer. 2009 Apr;9(4):274-84 PMID: 19308067
  41. Independent association of lobular involution and mammographic breast density with breast cancer risk.
    J Natl Cancer Inst. 2010 Nov 17;102(22):1716-23 PMID: 21037116
  42. Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer.
    Ann Surg. 2004 Aug;240(2):306-12 PMID: 15273556
  43. Cancer stem cells: an old idea--a paradigm shift.
    Cancer Res. 2006 Feb 15;66(4):1883-90; discussion 1895-6 PMID: 16488983
  44. Biological and clinical considerations regarding the use of surgery and chemotherapy in the treatment of primary breast cancer.
    Cancer. 1977 Jul;40(1 Suppl):574-87 PMID: 328138
  45. Collagen density promotes mammary tumor initiation and progression.
    BMC Med. 2008 Apr 28;6:11 PMID: 18442412
  46. Genes that mediate breast cancer metastasis to the brain.
    Nature. 2009 Jun 18;459(7249):1005-9 PMID: 19421193
  47. Dose-intensified treatment of advanced-stage diffuse large B-cell lymphomas.
    Semin Hematol. 2006 Oct;43(4):221-9 PMID: 17027656
  48. Heritability of mammographic density, a risk factor for breast cancer.
    N Engl J Med. 2002 Sep 19;347(12):886-94 PMID: 12239257
  49. Development of purine-scaffold small molecule inhibitors of Hsp90.
    Curr Cancer Drug Targets. 2003 Oct;3(5):371-6 PMID: 14529388
  50. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years.
    Br J Cancer. 1957 Sep;11(3):359-77 PMID: 13499785
  51. ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis.
    Genes Dev. 2009 Aug 15;23(16):1882-94 PMID: 19608765
  52. MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer.
    Genes Dev. 2011 Feb 1;25(3):226-31 PMID: 21289068
  53. Effect of reresection in extremity soft tissue sarcoma.
    Ann Surg. 2000 May;231(5):655-63 PMID: 10767786
  54. Gene-expression signatures in breast cancer.
    N Engl J Med. 2009 Feb 19;360(8):790-800 PMID: 19228622
  55. Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process.
    Ann Oncol. 2005 Sep;16(9):1449-57 PMID: 15956037
  56. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models.
    Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18115-20 PMID: 20921380
  57. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice.
    Cell. 1988 Nov 18;55(4):619-25 PMID: 3180222
  58. Angiogenesis in cancer and other diseases.
    Nature. 2000 Sep 14;407(6801):249-57 PMID: 11001068
  59. Tumor suppressors and cell metabolism: a recipe for cancer growth.
    Genes Dev. 2009 Mar 1;23(5):537-48 PMID: 19270154
  60. Is cancer a disease of self-seeding?
    Nat Med. 2006 Aug;12(8):875-8 PMID: 16892025
  61. Hereditary cancer predisposition syndromes.
    J Clin Oncol. 2005 Jan 10;23(2):276-92 PMID: 15637391
  62. A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications.
    Cancer Res. 2003 Apr 15;63(8):1727-30 PMID: 12702551
Article Info
Journal
Nature reviews. Clinical oncology
Abbr.
Nat Rev Clin Oncol
ISSN
1759-4782
DOI
10.1038/nrclinonc.2011.64
Published
2011-06-00
Epub
2011-00-26
Pages
369-77
Language
English
Region
England
NLM ID
101500077
Subset
IM
External Links
PubMed source DOI: 10.1038/nrclinonc.2011.64 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2