Autocrine Effects of Tumor-Derived Complement

Min Soon Cho; Hernan G. Vasquez; Rajesha Rupaimoole; Sunila Pradeep; Sherry Wu; Behrouz Zand; Hee Dong Han; Cristian Rodriguez-Aguayo; Justin Bottsford-Miller; Jie Huang; Takahito Miyake; Hyun Jin Choi; Heather J. Dalton; Cristina Ivan; Keith Baggerly; Gabriel Lopez-Berestein; Anil K. Sood; Vahid Afshar-Kharghan

doi:10.1016/j.celrep.2014.02.014

Autocrine Effects of Tumor-Derived Complement

Min Soon Cho, Hernan G. Vasquez, Rajesha Rupaimoole, Sunila Pradeep, Sherry Wu, Behrouz Zand, Hee Dong Han, Cristian Rodriguez-Aguayo, Justin Bottsford-Miller, Jie Huang, Takahito Miyake, Hyun Jin Choi, Heather J. Dalton, Cristina Ivan, Keith Baggerly, Gabriel Lopez-Berestein, Anil K. Sood, Vahid Afshar-Kharghan

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154 Scopus citations

Abstract

We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic Tcells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene incancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

Original language	English (US)
Pages (from-to)	1085-1095
Number of pages	11
Journal	Cell Reports
Volume	6
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2014.02.014
State	Published - Mar 27 2014

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

Bioinformatics Shared Resource
Flow Cytometry and Cellular Imaging Facility
Research Animal Support Facility
Clinical Trials Office

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10.1016/j.celrep.2014.02.014

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Cho, M. S., Vasquez, H. G., Rupaimoole, R., Pradeep, S., Wu, S., Zand, B., Han, H. D., Rodriguez-Aguayo, C., Bottsford-Miller, J., Huang, J., Miyake, T., Choi, H. J., Dalton, H. J., Ivan, C., Baggerly, K., Lopez-Berestein, G., Sood, A. K., & Afshar-Kharghan, V. (2014). Autocrine Effects of Tumor-Derived Complement. Cell Reports, 6(6), 1085-1095. https://doi.org/10.1016/j.celrep.2014.02.014

Cho, MS, Vasquez, HG, Rupaimoole, R, Pradeep, S, Wu, S, Zand, B, Han, HD, Rodriguez-Aguayo, C, Bottsford-Miller, J, Huang, J, Miyake, T, Choi, HJ, Dalton, HJ, Ivan, C, Baggerly, K, Lopez-Berestein, G , Sood, AK & Afshar-Kharghan, V 2014, 'Autocrine Effects of Tumor-Derived Complement', Cell Reports, vol. 6, no. 6, pp. 1085-1095. https://doi.org/10.1016/j.celrep.2014.02.014

@article{1f7ade55465a4433ac52a5414601e7fa,

title = "Autocrine Effects of Tumor-Derived Complement",

abstract = "We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic Tcells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene incancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.",

author = "Cho, {Min Soon} and Vasquez, {Hernan G.} and Rajesha Rupaimoole and Sunila Pradeep and Sherry Wu and Behrouz Zand and Han, {Hee Dong} and Cristian Rodriguez-Aguayo and Justin Bottsford-Miller and Jie Huang and Takahito Miyake and Choi, {Hyun Jin} and Dalton, {Heather J.} and Cristina Ivan and Keith Baggerly and Gabriel Lopez-Berestein and Sood, {Anil K.} and Vahid Afshar-Kharghan",

note = "Funding Information: We would like to thank Donna Reynolds and Robert Langley for their guidance with immunohistochemistry studies. B.Z., J.B.-M., and H.j.C. were supported by an NIH T32 Training Grant CA101642. This work was also supported in part by NIH grants (P50CA083639, CA109298, P50CA098258, P30CA016672, UH2TR000943, U54CA151668, U54CA96300, U54CA96297, and R01CA177909), CPRIT RP110595, Ovarian Cancer Research Fund Program Project Development Grant, Department of Defense (OC073399, OC120547, and OC100237), the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, and the Blanton-Davis Ovarian Cancer Research Program. ",

year = "2014",

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doi = "10.1016/j.celrep.2014.02.014",

language = "English (US)",

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AU - Cho, Min Soon

AU - Vasquez, Hernan G.

AU - Rupaimoole, Rajesha

AU - Pradeep, Sunila

AU - Wu, Sherry

AU - Zand, Behrouz

AU - Han, Hee Dong

AU - Rodriguez-Aguayo, Cristian

AU - Bottsford-Miller, Justin

AU - Huang, Jie

AU - Miyake, Takahito

AU - Choi, Hyun Jin

AU - Dalton, Heather J.

AU - Ivan, Cristina

AU - Baggerly, Keith

AU - Lopez-Berestein, Gabriel

AU - Sood, Anil K.

AU - Afshar-Kharghan, Vahid

N1 - Funding Information: We would like to thank Donna Reynolds and Robert Langley for their guidance with immunohistochemistry studies. B.Z., J.B.-M., and H.j.C. were supported by an NIH T32 Training Grant CA101642. This work was also supported in part by NIH grants (P50CA083639, CA109298, P50CA098258, P30CA016672, UH2TR000943, U54CA151668, U54CA96300, U54CA96297, and R01CA177909), CPRIT RP110595, Ovarian Cancer Research Fund Program Project Development Grant, Department of Defense (OC073399, OC120547, and OC100237), the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, and the Blanton-Davis Ovarian Cancer Research Program.

PY - 2014/3/27

Y1 - 2014/3/27

N2 - We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic Tcells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene incancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

AB - We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic Tcells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene incancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

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Autocrine Effects of Tumor-Derived Complement

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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