title: Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis.
abstract: BACKGROUND
  Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.
  
  
  METHODS
  A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.
  
  
  RESULTS
  Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.
  
  
  CONCLUSIONS
  Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.
authors.affiliation: Department of Surgery, Biochemistry and Molecular Biology, University of Southern California, 1450 Biggy Street NRT6501, Los Angeles, CA 90033, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Choi
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: N Y
authors.initials: NY
authors.lastname: Kim
authors.forename: V
authors.initials: V
authors.lastname: Khatchadourian
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: H K
authors.initials: HK
authors.lastname: Chung
authors.forename: D
authors.initials: D
authors.lastname: Choi
authors.forename: M J
authors.initials: MJ
authors.lastname: LaBonte
authors.forename: R D
authors.initials: RD
authors.lastname: Ladner
authors.forename: K C
authors.initials: KC
authors.lastname: Nagulapalli Venkata
authors.forename: D O
authors.initials: DO
authors.lastname: Rosenberg
authors.forename: N A
authors.initials: NA
authors.lastname: Petasis
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Y-K
authors.initials: YK
authors.lastname: Hong
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059016:Tumor Microenvironment
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B