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Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion

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Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion. / Conn, Erin M; Bøtkjær, Kenneth Alrø; Kupriyanova, Tatyana A; Andreasen, Peter A; Deryugina, Elena I; Quigley, James P.

In: American Journal of Pathology, Vol. 175, No. 4, 01.10.2009, p. 1638-52.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Conn, EM, Bøtkjær, KA, Kupriyanova, TA, Andreasen, PA, Deryugina, EI & Quigley, JP 2009, 'Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion', American Journal of Pathology, vol. 175, no. 4, pp. 1638-52. https://doi.org/10.2353/ajpath.2009.090384

APA

Conn, E. M., Bøtkjær, K. A., Kupriyanova, T. A., Andreasen, P. A., Deryugina, E. I., & Quigley, J. P. (2009). Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion. American Journal of Pathology, 175(4), 1638-52. https://doi.org/10.2353/ajpath.2009.090384

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MLA

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Author

Conn, Erin M ; Bøtkjær, Kenneth Alrø ; Kupriyanova, Tatyana A ; Andreasen, Peter A ; Deryugina, Elena I ; Quigley, James P. / Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion. In: American Journal of Pathology. 2009 ; Vol. 175, No. 4. pp. 1638-52.

Bibtex

@article{0dfc9c6310054462b9eac2432309e12a,
title = "Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion",
abstract = "To analyze the process of tumor cell intravasation, we used the human tumor-chick embryo spontaneous metastasis model to select in vivo high (PC-hi/diss) and low (PC-lo/diss) disseminating variants from the human PC-3 prostate carcinoma cell line. These variants dramatically differed in their intravasation and dissemination capacities in both chick embryo and mouse spontaneous metastasis models. Concomitant with enhanced intravasation, PC-hi/diss exhibited increased angiogenic potential in avian and murine models. PC-hi/diss angiogenesis and intravasation were dependent on increased secretion of vascular endothelial growth factor (VEGF), since treating developing tumors with a function-blocking anti-VEGF antibody simultaneously inhibited both processes without affecting primary tumor growth. PC-hi/diss cells were also more migratory and invasive, suggestive of heightened ability to escape from primary tumors due to matrix-degrading activity. Consistent with this suggestion, PC-hi/diss cells produced more of the serine protease urokinase-type plasminogen activator (uPA) as compared with PC-lo/diss. The functional role of uPA in PC-hi/diss dissemination was confirmed by inhibition of invasion, angiogenesis, and intravasation with specific function-blocking antibodies that prevented uPA activation and blocked uPA activity. These processes were similarly sensitive to aprotinin, a potent inhibitor of serine proteases, including uPA-generated plasmin. Thus, our comparison of the PC-3 intravasation variants points to key roles for the uPA-plasmin system in PC-hi/diss intravasation, possibly via (1) promoting tumor cell matrix invasion and (2) facilitating development of VEGF-dependent angiogenic blood vessels.",
keywords = "Animals, Cell Adhesion, Cell Line, Tumor, Cell Movement, Chick Embryo, Disease Models, Animal, Humans, Male, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Neovascularization, Pathologic, Prostatic Neoplasms, Urokinase-Type Plasminogen Activator, Vascular Endothelial Growth Factor A",
author = "Conn, {Erin M} and B{\o}tkj{\ae}r, {Kenneth Alr{\o}} and Kupriyanova, {Tatyana A} and Andreasen, {Peter A} and Deryugina, {Elena I} and Quigley, {James P}",
year = "2009",
month = oct,
day = "1",
doi = "10.2353/ajpath.2009.090384",
language = "English",
volume = "175",
pages = "1638--52",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion

AU - Conn, Erin M

AU - Bøtkjær, Kenneth Alrø

AU - Kupriyanova, Tatyana A

AU - Andreasen, Peter A

AU - Deryugina, Elena I

AU - Quigley, James P

PY - 2009/10/1

Y1 - 2009/10/1

N2 - To analyze the process of tumor cell intravasation, we used the human tumor-chick embryo spontaneous metastasis model to select in vivo high (PC-hi/diss) and low (PC-lo/diss) disseminating variants from the human PC-3 prostate carcinoma cell line. These variants dramatically differed in their intravasation and dissemination capacities in both chick embryo and mouse spontaneous metastasis models. Concomitant with enhanced intravasation, PC-hi/diss exhibited increased angiogenic potential in avian and murine models. PC-hi/diss angiogenesis and intravasation were dependent on increased secretion of vascular endothelial growth factor (VEGF), since treating developing tumors with a function-blocking anti-VEGF antibody simultaneously inhibited both processes without affecting primary tumor growth. PC-hi/diss cells were also more migratory and invasive, suggestive of heightened ability to escape from primary tumors due to matrix-degrading activity. Consistent with this suggestion, PC-hi/diss cells produced more of the serine protease urokinase-type plasminogen activator (uPA) as compared with PC-lo/diss. The functional role of uPA in PC-hi/diss dissemination was confirmed by inhibition of invasion, angiogenesis, and intravasation with specific function-blocking antibodies that prevented uPA activation and blocked uPA activity. These processes were similarly sensitive to aprotinin, a potent inhibitor of serine proteases, including uPA-generated plasmin. Thus, our comparison of the PC-3 intravasation variants points to key roles for the uPA-plasmin system in PC-hi/diss intravasation, possibly via (1) promoting tumor cell matrix invasion and (2) facilitating development of VEGF-dependent angiogenic blood vessels.

AB - To analyze the process of tumor cell intravasation, we used the human tumor-chick embryo spontaneous metastasis model to select in vivo high (PC-hi/diss) and low (PC-lo/diss) disseminating variants from the human PC-3 prostate carcinoma cell line. These variants dramatically differed in their intravasation and dissemination capacities in both chick embryo and mouse spontaneous metastasis models. Concomitant with enhanced intravasation, PC-hi/diss exhibited increased angiogenic potential in avian and murine models. PC-hi/diss angiogenesis and intravasation were dependent on increased secretion of vascular endothelial growth factor (VEGF), since treating developing tumors with a function-blocking anti-VEGF antibody simultaneously inhibited both processes without affecting primary tumor growth. PC-hi/diss cells were also more migratory and invasive, suggestive of heightened ability to escape from primary tumors due to matrix-degrading activity. Consistent with this suggestion, PC-hi/diss cells produced more of the serine protease urokinase-type plasminogen activator (uPA) as compared with PC-lo/diss. The functional role of uPA in PC-hi/diss dissemination was confirmed by inhibition of invasion, angiogenesis, and intravasation with specific function-blocking antibodies that prevented uPA activation and blocked uPA activity. These processes were similarly sensitive to aprotinin, a potent inhibitor of serine proteases, including uPA-generated plasmin. Thus, our comparison of the PC-3 intravasation variants points to key roles for the uPA-plasmin system in PC-hi/diss intravasation, possibly via (1) promoting tumor cell matrix invasion and (2) facilitating development of VEGF-dependent angiogenic blood vessels.

KW - Animals

KW - Cell Adhesion

KW - Cell Line, Tumor

KW - Cell Movement

KW - Chick Embryo

KW - Disease Models, Animal

KW - Humans

KW - Male

KW - Mice

KW - Neoplasm Invasiveness

KW - Neoplasm Metastasis

KW - Neovascularization, Pathologic

KW - Prostatic Neoplasms

KW - Urokinase-Type Plasminogen Activator

KW - Vascular Endothelial Growth Factor A

U2 - 10.2353/ajpath.2009.090384

DO - 10.2353/ajpath.2009.090384

M3 - Journal article

C2 - 19729488

VL - 175

SP - 1638

EP - 1652

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -