Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor

Woo Nam Suk Woo Nam, T. Clair, Young Sik Kim, A. McMarlin, E. Schiffmann, L. A. Liotta, M. L. Stracke

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Autotaxin [ATX (NPP-2)], originally isolated as a tumor motility-stimulating protein, has recently been shown to augment tumor aggressiveness. Specifically, atx-transfected, ras-transformed NIH3T3 cell lines have been shown to be more invasive, tumorigenic, and metastatic than mock-transfected ras-transformed control cells. In addition, the atx-transfected ras-transformed cell lines appeared to produce tumors that were much more hyperemic than those formed by appropriate control cells. This observation led to the present study, in which we demonstrate that ATX modulates angiogenesis both directly and indirectly. We have used a murine in vivo angiogenesis model in which treated Matrigel plugs are injected s.c. into athymic nude BALB/c mice. Using the same transfected cell lines as before, we found that mixing atx-transfected ras-transformed NIH3T3 cells into the Matrigel resulted in greater new blood vessel formation than control cells. Similarly, mixing purified ATX into the Matrigel resulted in new blood vessel formation within the plug, similar to that produced by vascular endothelial growth factor. Mechanistically, ATX is not a strong chemoattractant for human endothelial cells (HUVECs); however, it strongly stimulates motility in human coronary artery smooth muscle cells. In addition, ATX stimulates HUVECs grown on Matrigel to form tubules, much like vascular endothelial growth factor. Both of these normal cell types are shown to express and secrete ATX. In HUVECs, ATX expression is up-regulated by basic fibroblast growth factor in a time-dependent manner. This up-regulation also extends to secretion of enzymatically active protein, as demonstrated by Western blot analysis and quantification of type-1 phosphodiesterase activity. These results establish the presence of ATX in HUVECs and coronary artery smooth muscle cells and specify ATX as a novel angiogenic factor, suggesting that ATX could contribute to the metastatic cascade through multiple mechanisms, perhaps by supporting an invasive microenvironment for both normal and tumor cells.

Original languageEnglish
Pages (from-to)6938-6944
Number of pages7
JournalCancer Research
Volume61
Issue number18
Publication statusPublished - 2001 Sep 15
Externally publishedYes

Fingerprint

Angiogenesis Inducing Agents
Neoplasm Metastasis
Transformed Cell Line
Vascular Endothelial Growth Factor A
Smooth Muscle Myocytes
Blood Vessels
Neoplasms
Coronary Vessels
Molecular Motor Proteins
Chemotactic Factors
Phosphoric Diester Hydrolases
Fibroblast Growth Factor 2
Up-Regulation
Endothelial Cells
Western Blotting
Cell Line
matrigel
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suk Woo Nam, W. N., Clair, T., Kim, Y. S., McMarlin, A., Schiffmann, E., Liotta, L. A., & Stracke, M. L. (2001). Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Research, 61(18), 6938-6944.

Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. / Suk Woo Nam, Woo Nam; Clair, T.; Kim, Young Sik; McMarlin, A.; Schiffmann, E.; Liotta, L. A.; Stracke, M. L.

In: Cancer Research, Vol. 61, No. 18, 15.09.2001, p. 6938-6944.

Research output: Contribution to journalArticle

Suk Woo Nam, WN, Clair, T, Kim, YS, McMarlin, A, Schiffmann, E, Liotta, LA & Stracke, ML 2001, 'Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor', Cancer Research, vol. 61, no. 18, pp. 6938-6944.
Suk Woo Nam WN, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA et al. Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Research. 2001 Sep 15;61(18):6938-6944.
Suk Woo Nam, Woo Nam ; Clair, T. ; Kim, Young Sik ; McMarlin, A. ; Schiffmann, E. ; Liotta, L. A. ; Stracke, M. L. / Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. In: Cancer Research. 2001 ; Vol. 61, No. 18. pp. 6938-6944.
@article{50d26dad3904439a8835ec431fe14398,
title = "Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor",
abstract = "Autotaxin [ATX (NPP-2)], originally isolated as a tumor motility-stimulating protein, has recently been shown to augment tumor aggressiveness. Specifically, atx-transfected, ras-transformed NIH3T3 cell lines have been shown to be more invasive, tumorigenic, and metastatic than mock-transfected ras-transformed control cells. In addition, the atx-transfected ras-transformed cell lines appeared to produce tumors that were much more hyperemic than those formed by appropriate control cells. This observation led to the present study, in which we demonstrate that ATX modulates angiogenesis both directly and indirectly. We have used a murine in vivo angiogenesis model in which treated Matrigel plugs are injected s.c. into athymic nude BALB/c mice. Using the same transfected cell lines as before, we found that mixing atx-transfected ras-transformed NIH3T3 cells into the Matrigel resulted in greater new blood vessel formation than control cells. Similarly, mixing purified ATX into the Matrigel resulted in new blood vessel formation within the plug, similar to that produced by vascular endothelial growth factor. Mechanistically, ATX is not a strong chemoattractant for human endothelial cells (HUVECs); however, it strongly stimulates motility in human coronary artery smooth muscle cells. In addition, ATX stimulates HUVECs grown on Matrigel to form tubules, much like vascular endothelial growth factor. Both of these normal cell types are shown to express and secrete ATX. In HUVECs, ATX expression is up-regulated by basic fibroblast growth factor in a time-dependent manner. This up-regulation also extends to secretion of enzymatically active protein, as demonstrated by Western blot analysis and quantification of type-1 phosphodiesterase activity. These results establish the presence of ATX in HUVECs and coronary artery smooth muscle cells and specify ATX as a novel angiogenic factor, suggesting that ATX could contribute to the metastatic cascade through multiple mechanisms, perhaps by supporting an invasive microenvironment for both normal and tumor cells.",
author = "{Suk Woo Nam}, {Woo Nam} and T. Clair and Kim, {Young Sik} and A. McMarlin and E. Schiffmann and Liotta, {L. A.} and Stracke, {M. L.}",
year = "2001",
month = "9",
day = "15",
language = "English",
volume = "61",
pages = "6938--6944",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

TY - JOUR

T1 - Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor

AU - Suk Woo Nam, Woo Nam

AU - Clair, T.

AU - Kim, Young Sik

AU - McMarlin, A.

AU - Schiffmann, E.

AU - Liotta, L. A.

AU - Stracke, M. L.

PY - 2001/9/15

Y1 - 2001/9/15

N2 - Autotaxin [ATX (NPP-2)], originally isolated as a tumor motility-stimulating protein, has recently been shown to augment tumor aggressiveness. Specifically, atx-transfected, ras-transformed NIH3T3 cell lines have been shown to be more invasive, tumorigenic, and metastatic than mock-transfected ras-transformed control cells. In addition, the atx-transfected ras-transformed cell lines appeared to produce tumors that were much more hyperemic than those formed by appropriate control cells. This observation led to the present study, in which we demonstrate that ATX modulates angiogenesis both directly and indirectly. We have used a murine in vivo angiogenesis model in which treated Matrigel plugs are injected s.c. into athymic nude BALB/c mice. Using the same transfected cell lines as before, we found that mixing atx-transfected ras-transformed NIH3T3 cells into the Matrigel resulted in greater new blood vessel formation than control cells. Similarly, mixing purified ATX into the Matrigel resulted in new blood vessel formation within the plug, similar to that produced by vascular endothelial growth factor. Mechanistically, ATX is not a strong chemoattractant for human endothelial cells (HUVECs); however, it strongly stimulates motility in human coronary artery smooth muscle cells. In addition, ATX stimulates HUVECs grown on Matrigel to form tubules, much like vascular endothelial growth factor. Both of these normal cell types are shown to express and secrete ATX. In HUVECs, ATX expression is up-regulated by basic fibroblast growth factor in a time-dependent manner. This up-regulation also extends to secretion of enzymatically active protein, as demonstrated by Western blot analysis and quantification of type-1 phosphodiesterase activity. These results establish the presence of ATX in HUVECs and coronary artery smooth muscle cells and specify ATX as a novel angiogenic factor, suggesting that ATX could contribute to the metastatic cascade through multiple mechanisms, perhaps by supporting an invasive microenvironment for both normal and tumor cells.

AB - Autotaxin [ATX (NPP-2)], originally isolated as a tumor motility-stimulating protein, has recently been shown to augment tumor aggressiveness. Specifically, atx-transfected, ras-transformed NIH3T3 cell lines have been shown to be more invasive, tumorigenic, and metastatic than mock-transfected ras-transformed control cells. In addition, the atx-transfected ras-transformed cell lines appeared to produce tumors that were much more hyperemic than those formed by appropriate control cells. This observation led to the present study, in which we demonstrate that ATX modulates angiogenesis both directly and indirectly. We have used a murine in vivo angiogenesis model in which treated Matrigel plugs are injected s.c. into athymic nude BALB/c mice. Using the same transfected cell lines as before, we found that mixing atx-transfected ras-transformed NIH3T3 cells into the Matrigel resulted in greater new blood vessel formation than control cells. Similarly, mixing purified ATX into the Matrigel resulted in new blood vessel formation within the plug, similar to that produced by vascular endothelial growth factor. Mechanistically, ATX is not a strong chemoattractant for human endothelial cells (HUVECs); however, it strongly stimulates motility in human coronary artery smooth muscle cells. In addition, ATX stimulates HUVECs grown on Matrigel to form tubules, much like vascular endothelial growth factor. Both of these normal cell types are shown to express and secrete ATX. In HUVECs, ATX expression is up-regulated by basic fibroblast growth factor in a time-dependent manner. This up-regulation also extends to secretion of enzymatically active protein, as demonstrated by Western blot analysis and quantification of type-1 phosphodiesterase activity. These results establish the presence of ATX in HUVECs and coronary artery smooth muscle cells and specify ATX as a novel angiogenic factor, suggesting that ATX could contribute to the metastatic cascade through multiple mechanisms, perhaps by supporting an invasive microenvironment for both normal and tumor cells.

UR - http://www.scopus.com/inward/record.url?scp=0035884290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035884290&partnerID=8YFLogxK

M3 - Article

VL - 61

SP - 6938

EP - 6944

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 18

ER -