title: Hyaluronan expression in primary and secondary brain tumors.
abstract: BACKGROUND
  Collectively, primary and secondary brain tumors represent a major public health challenge. Glioblastoma (GBM) is the most common primary brain tumor in adults and is associated with a dismal 5-year survival of only 10%. Breast cancer causes secondary tumors; it occurs in 200,000 patients yearly and 30% of these individuals develop brain metastases which also lead to a very poor prognosis. GBM and primary breast tumors are known to express hyaluronan (HA) which may serve as a therapeutic target.
  
  
  METHODS
  For the present study we had two aims: (I) to identify suitable preclinical models for HA in GBM by examining HA expression in human GBM cell lines implanted orthotopically in mice; and (II) to determine whether breast cancer brain metastases in human patients express HA similar to the primary tumor. Forty human surgical samples of primary breast tumors and breast cancer brain metastases were processed and stained for HA. Athymic nu/nu mice were orthotopically implanted with one of 15 GBM lines and after tumors were established, quantitative immunohistochemistry determined whether.
  
  
  RESULTS
  HA was expressed. All GBM cell lines and patient-derived orthotopic tumors did express HA, with 3 primary human lines expressing the highest staining intensity, above that of normal brain. All 40 human primary breast tumors and brain metastases examined also contained HA, though staining intensity was highly variable.
  
  
  CONCLUSIONS
  Our data support the use of specific patient-derived GBM cell lines in nu/nu mice for preclinical studies on HA-targeting therapies. Additionally, our research provides a basis for the assessment of HA expression and HA-targeting therapeutic agents for the treatment of breast cancer brain metastases.
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Jadin
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pastorino
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Symons
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nomura
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Juarez
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Makale
authors.affiliation: 1 Halozyme Therapeutics Inc., San Diego, CA, USA ; 2 Translational Neuro-Oncology Laboratories, Moores Cancer Center, 3 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
keywords: Hyaluronan (HA); breast cancer; glioblastoma (GBM); primary brain tumor; secondary brain tumor