Enhanced tumor growth in the NaS1 sulfate transporter null mouse
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Enhanced tumor growth in the NaS1 sulfate transporter null mouse. / Dawson, Paul Anthony; Choyce, Allison; Chuang, Christine; Whitelock, John; Markovich, Daniel; Leggatt, Graham Robert.
In: Cancer Science (Print), Vol. 101, No. 2, 02.2010, p. 369-73.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Enhanced tumor growth in the NaS1 sulfate transporter null mouse
AU - Dawson, Paul Anthony
AU - Choyce, Allison
AU - Chuang, Christine
AU - Whitelock, John
AU - Markovich, Daniel
AU - Leggatt, Graham Robert
PY - 2010/2
Y1 - 2010/2
N2 - Sulfate plays an important role in maintaining normal structure and function of tissues, and its content is decreased in certain cancers including lung carcinoma. In this study, we investigated tumor growth in a mouse model of hyposulfatemia (Nas1(-/-)) and compared it to wild-type (Nas1(+/+)) mice. Lung epithelial tumor cells (TC-1 cell line) were injected subcutaneously into male Nas1(-/-) and Nas1(+/+) mice on a mixed 129Sv and C57BL/6 genetic background. Tumor sections were stained with anti-glycosaminoglycan antibodies to assess the distribution of proteoglycans and Gomori's trichrome to detect collagen. After 14 days, tumor weights were markedly increased (by approximately 12-fold) in Nas1(-/-) mice when compared with Nas1(+/+) mice. Histological analyses of tumors revealed increased (by approximately 2.4-fold) vessel content, as well as markedly reduced collagen and immunoreactivity against glycosaminoglycan structural epitopes in the tumors from Nas1(-/-) mice. No significant differences were found for the growth of cultured TC-1 cells supplemented with Nas1(-/-) or Nas1(+/+) serum, as determined by (3)H-thymidine incorporation, implying that the cell culture conditions may not reflect the in vivo situation of enhanced tumor growth. This study has revealed increased tumor growth and an altered extracellular tumor matrix in hyposulfatemic Nas1(-/-) mice. These findings highlight the importance of blood sulfate levels as a possible modulator of tumor growth, and could lead to future cancer studies in humans with altered sulfate homeostasis.
AB - Sulfate plays an important role in maintaining normal structure and function of tissues, and its content is decreased in certain cancers including lung carcinoma. In this study, we investigated tumor growth in a mouse model of hyposulfatemia (Nas1(-/-)) and compared it to wild-type (Nas1(+/+)) mice. Lung epithelial tumor cells (TC-1 cell line) were injected subcutaneously into male Nas1(-/-) and Nas1(+/+) mice on a mixed 129Sv and C57BL/6 genetic background. Tumor sections were stained with anti-glycosaminoglycan antibodies to assess the distribution of proteoglycans and Gomori's trichrome to detect collagen. After 14 days, tumor weights were markedly increased (by approximately 12-fold) in Nas1(-/-) mice when compared with Nas1(+/+) mice. Histological analyses of tumors revealed increased (by approximately 2.4-fold) vessel content, as well as markedly reduced collagen and immunoreactivity against glycosaminoglycan structural epitopes in the tumors from Nas1(-/-) mice. No significant differences were found for the growth of cultured TC-1 cells supplemented with Nas1(-/-) or Nas1(+/+) serum, as determined by (3)H-thymidine incorporation, implying that the cell culture conditions may not reflect the in vivo situation of enhanced tumor growth. This study has revealed increased tumor growth and an altered extracellular tumor matrix in hyposulfatemic Nas1(-/-) mice. These findings highlight the importance of blood sulfate levels as a possible modulator of tumor growth, and could lead to future cancer studies in humans with altered sulfate homeostasis.
KW - Animals
KW - Cation Transport Proteins
KW - Cell Proliferation
KW - Collagen
KW - Glycosaminoglycans
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neoplasms, Experimental
KW - Sulfates
KW - Symporters
U2 - 10.1111/j.1349-7006.2009.01399.x
DO - 10.1111/j.1349-7006.2009.01399.x
M3 - Journal article
C2 - 19895604
VL - 101
SP - 369
EP - 373
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 2
ER -
ID: 162757831