UNIVERSITAS AIRLANGGA



Detail Article

Indonesian Journal of Clinical Pathology and Medical Laboratory

ISSN 0854-4263

Vol. 19 / No. 2 / Published : 2013-01

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Original Article :

C-x-c receptor 4 (cxcr4) in metastasis of breast cancer

Author :

  1. I Wayan Sudarsa*1
  2. I WayanPutuSutirtaYasa*2
  1. Divisi Bedah Onkologi, Departemen Bedah FK Unud/RSUP Sanglah Denpasar,Pascasarjana Universitas Udayana
  2. Departemen Patologi Klinik FK Unud/RSUP Sanglah Denpasar, Pascasarjana Universitas Udayana

Abstract :

The chemokine receptors CXCR4 (chemokine C-X-C motif receptor 4) and its ligand (stromal derived factor-1/SDF-1 or chemokine  motif ligand 12/ CXCL12) play an important role in cancer invasion and metastasis. The spread of breast cancer follows a nonrandom metastatic pattern typically involving spread of tumor to regional lymph nodes, lung, liver, and/or bone marrow. The ligand for CXCR4, SDF-1/CXCL12, is highly expressed by stromal fibroblasts within these tissues. The chemokine receptors CXCR4 is structurally related to chemokine receptor belonging to the superfamily of the seven transmembrane G-protein coupled receptors. In contrast to normal breast tissue, breast cancer cells typically express high levels of functional CXCR4 receptors that can direct chemotaxis and invasive responses. Expression of SDF-1/ CXCL-12 in turn, promotes the progression of breast cancer by directly enhancing tumor-cell growth and by recruiting endothelial progenitor cells that are required for tumor angiogenesis. High-level expression of CXCR4 on neoplastic cells is associated with relatively poor overall survival and bad prognosis in patients with breast cancer. The promising results in the preclinical tumor models indicate that CXCR4 antagonists may have to reduce the spread of cancer that is called anti tumor activity in patients with breast cancer. The chemokine receptors CXCR4 antagonists, although initially developed for treatment of acquired  immunodeficiency diseases syndrome (AIDS), actually may become effective agents as a molecular targeted therapy for breast cancer.     Reseptor kemokin C-X-C(CXCR4) dan ligandnya (stromal derived factor-1/SDF-1 atau chemokine motif ligand 12/ CXCL12) memegang peran penting dalam proses kanker memasuki (invasi) dan menyebar (metastasis). Penyebaran kanker payudara mengikuti pola metastasis yang bersifat non random yang biasanya secara khusus menuju ke kelenjar getah bening regional, paru, hati dan atau ke sumsum tulang. Protein SDF-1/CXCL12 yang merupakan ligand dari CXCR4 diekspresikan secara berlebihan di organ tersebut. Secara struktural reseptor kemokin CXCR4 merupakan keluarga kelompok reseptor the seven transmembrane G-protein coupled receptors. Berbeda dengan sel jaringan payudara normal, sel kanker payudara secara khusus mengekspresikan reseptor CXCR4 dengan kadar yang tinggi, sebagai respons langsung terhadap kemotaksis dan penyerbuan. Sebaliknya ekspresi SDF-1/CXCL12 dapat merangsang kemajuan kanker payudara secara langsung dengan meningkatkan pertumbuhan sel dan dengan menarik endothelial progenitor cells yang diperlukan untuk angiogenesis tumor. Sel kanker payudara yang mengekspresikan reseptor kemokin CXCR4 yang tinggi berhubungan dengan ramalan jalannya penyakit yang relatif buruk dan angka bertahan hidup yang rendah di penderita kanker payudara. Kajian preklinik di model sel tumor menunjukkan bahwa pemberian antibodi monoklon antagonis CXCR4 beraktivitas mengurangi penyebaran kanker, sehingga disebut sebagai anti kanker dan menjanjikan di masa yang akan datang pada pengobatan kanker payudara. Zat antagonis CXCR4 walaupun pada awalnya dikembangkan untuk pengobatan penderita human immunodeficiency virus (HIV) atau acquired immunodeficiency diseases syndrome (AIDS), kenyataannya juga dapat dipakai sebagai molecular targeted therapy terhadap kanker payudara.

Keyword :

CXCR4, SDF-1/CXCL12-CXCR4 axis, breast cancer, metastasis,


References :

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al,(2009) Cancer Statistics USA : CA Cancer J Clin

Disis ML,(2005) Global Role of the Immune System in Identifying Cancer Initiation and Limiting Disease Progression USA : J Clin Oncol

3. Bracke ME, De Maeseneer D, van Mark V, Derycke L, Vanhoecke B, De Wever O, et al,(2008) Cell Motility and Breast Cancer Metastasis London : Springer

Burger JA, Kipps TJ,(2006) CXCR4: A Key Receptor in the Crosstalk Between Tumor Cells and their Microenvirontment USA : Blood

5. Liu Y., Ji R, Li J, Gu Q, Zhao X, Tao Sun T, et al,(2010) Correlation Effect of EGFR and CXCR4 and CCR7 Chemokine Receptors in Predicting Breast Cancer Metastasis and Prognosis USA : Journal of Experimental & Clinical Cancer Research





Archive Article

Cover Media Content

Volume : 19 / No. : 2 / Pub. : 2013-01
  1. Clinical Manifestion Sepsis And Nitric Oxide Level On Mice Induced By Lipopolysaccharide
  2. Gandarusa (justicia Gendarussa Burm.f.) Water And Expression Of Hyaluronidase Gene By Pcr Analysis
  3. Proteinuria In Stroke With And Without Diabetic
  4. The Stewart’s Approach In Blood Ph Underlying Metabolic Acidosis
  5. Microbes And Antimicrobial Sensitivity In Open Fracture
  6. Katekin From Green Tea Leaves (camellia Sinensis) To Malondialdehyde (mda) And Super Oxide Dismutase (sod)
  7. Procalcitonin And Interleukin-6 In Sepsis Systemic Inflammatory Response Syndrome (sirs)
  8. Gram Negative And Gram Positive Aerobic Bacteria Identification Using Conventional And Automatic Method
  9. Immature Platelet Fraction (ipf) And Thrombopoietin In Liver Cirrhosis
  10. Eosinopenia And Procalcitonin In Sepsis
  11. C-x-c Receptor 4 (cxcr4) In Metastasis Of Breast Cancer
  12. Hairy Cell Leukaemia

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