title: HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro.
abstract: BACKGROUND
  We identified two 3p21.3 regions (LUCA and AP20) as most frequently affected in lung, breast and other carcinomas and reported their fine physical and gene maps. It is becoming increasingly clear that each of these two regions contains several TSGs. Until now TSGs which were isolated from AP20 and LUCA regions (e.g.G21/NPRL2, RASSF1A, RASSF1C, SEMA3B, SEMA3F, RBSP3) were shown to inhibit tumour cell growth both in vitro and in vivo.
  
  
  RESULTS
  The effect of expression HYAL1 and HYAL2 was studied by colony formation inhibition, growth curve and cell proliferation tests in vitro and tumour growth assay in vivo. Very modest growth inhibition was detected in vitro in U2020 lung and KRC/Y renal carcinoma cell lines. In the in vivo experiment stably transfected KRC/Y cells expressing HYAL1 or HYAL2 were inoculated into SCID mice (10 and 12 mice respectively). Tumours grew in eight mice inoculated with HYAL1. Ectopic HYAL1 was deleted in all of them. HYAL2 was inoculated into 12 mice and only four tumours were obtained. In 3 of them the gene was deleted. In one tumour it was present but not expressed. As expected for tumour suppressor genes HYAL1 and HYAL2 were down-expressed in 15 fresh lung squamous cell carcinomas (100%) and clear cell RCC tumours (60-67%).
  
  
  CONCLUSIONS
  The results suggest that the expression of either gene has led to inhibition of tumour growth in vivo without noticeable effect on growth in vitro. HYAL1 and HYAL2 thus differ in this aspect from other tumour suppressors like P53 or RASSF1A that inhibit growth both in vitro and in vivo. Targeting the microenvironment of cancer cells is one of the most promising venues of cancer therapeutics. As major hyaluronidases in human cells, HYAL1 and HYAL2 may control intercellular interactions and microenvironment of tumour cells providing excellent targets for cancer treatment.
authors: Microbiology and Tumour Biology Center, Karolinska Institute, Stockholm, Sweden.
authors: Fuli
authors: F
authors: Wang
authors: Elvira V
authors: EV
authors: Grigorieva
authors: Jingfeng
authors: J
authors: Li
authors: Vera N
authors: VN
authors: Senchenko
authors: Tatiana V
authors: TV
authors: Pavlova
authors: Ekaterina A
authors: EA
authors: Anedchenko
authors: Anna V
authors: AV
authors: Kudryavtseva
authors: Alexander
authors: A
authors: Tsimanis
authors: Debora
authors: D
authors: Angeloni
authors: Michael I
authors: MI
authors: Lerman
authors: Vladimir I
authors: VI
authors: Kashuba
authors: George
authors: G
authors: Klein
authors: Eugene R
authors: ER
authors: Zabarovsky
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay / Q000379:methods; D058851:GPI-Linked Proteins; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000172:deficiency / Q000235:genetics* / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C473096:Hyal2 protein, human; C469220:Hyal1 protein, mouse; D006821:Hyaluronoglucosaminidase