Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted wilms' tumour

Harold N. Lovvorn, Rashmin C. Savani, Eduardo Ruchelli, Darrell L. Cass, N. Scott Adzick

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background/Purpose: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SClD) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. Results: Sera of mice supporting tumor growth had a median HA concentration of 9,379 μg/L (range, 459 to 3,206,176 μg/L) compared with a median HA concentration of 416 μg/L (range, 204 to 782 -g/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal- predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness. Copyright (C) 2000 W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)1070-1078
Number of pages9
JournalJournal of Pediatric Surgery
Volume35
Issue number7
DOIs
StatePublished - Jul 2000

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Wilms Tumor
Hyaluronic Acid
Heterografts
Histology
Serum
Neoplasms
Growth
SCID Mice
Subcutaneous Injections
Tumor Cell Line

Keywords

  • Heterotransplantation
  • Hyaluronan
  • SCID mouse
  • Tumor marker
  • Wilms' tumor

ASJC Scopus subject areas

  • Surgery

Cite this

Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted wilms' tumour. / Lovvorn, Harold N.; Savani, Rashmin C.; Ruchelli, Eduardo; Cass, Darrell L.; Adzick, N. Scott.

In: Journal of Pediatric Surgery, Vol. 35, No. 7, 07.2000, p. 1070-1078.

Research output: Contribution to journalArticle

Lovvorn, Harold N. ; Savani, Rashmin C. ; Ruchelli, Eduardo ; Cass, Darrell L. ; Adzick, N. Scott. / Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted wilms' tumour. In: Journal of Pediatric Surgery. 2000 ; Vol. 35, No. 7. pp. 1070-1078.
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abstract = "Background/Purpose: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SClD) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. Results: Sera of mice supporting tumor growth had a median HA concentration of 9,379 μg/L (range, 459 to 3,206,176 μg/L) compared with a median HA concentration of 416 μg/L (range, 204 to 782 -g/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal- predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness. Copyright (C) 2000 W.B. Saunders Company.",
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T1 - Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted wilms' tumour

AU - Lovvorn, Harold N.

AU - Savani, Rashmin C.

AU - Ruchelli, Eduardo

AU - Cass, Darrell L.

AU - Adzick, N. Scott

PY - 2000/7

Y1 - 2000/7

N2 - Background/Purpose: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SClD) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. Results: Sera of mice supporting tumor growth had a median HA concentration of 9,379 μg/L (range, 459 to 3,206,176 μg/L) compared with a median HA concentration of 416 μg/L (range, 204 to 782 -g/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal- predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness. Copyright (C) 2000 W.B. Saunders Company.

AB - Background/Purpose: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SClD) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. Results: Sera of mice supporting tumor growth had a median HA concentration of 9,379 μg/L (range, 459 to 3,206,176 μg/L) compared with a median HA concentration of 416 μg/L (range, 204 to 782 -g/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal- predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness. Copyright (C) 2000 W.B. Saunders Company.

KW - Heterotransplantation

KW - Hyaluronan

KW - SCID mouse

KW - Tumor marker

KW - Wilms' tumor

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