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C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

Author

Listed:
  • Roberta Bulla

    (University of Trieste)

  • Claudio Tripodo

    (University of Palermo)

  • Damiano Rami

    (University of Trieste)

  • Guang Sheng Ling

    (Centre for Complement and Inflammation Research, Imperial College)

  • Chiara Agostinis

    (Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo)

  • Carla Guarnotta

    (University of Palermo)

  • Sonia Zorzet

    (University of Trieste)

  • Paolo Durigutto

    (University of Trieste)

  • Marina Botto

    (Centre for Complement and Inflammation Research, Imperial College)

  • Francesco Tedesco

    (Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano)

Abstract

Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mice. Bone marrow (BM) chimeras between C1qa−/− and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth.

Suggested Citation

  • Roberta Bulla & Claudio Tripodo & Damiano Rami & Guang Sheng Ling & Chiara Agostinis & Carla Guarnotta & Sonia Zorzet & Paolo Durigutto & Marina Botto & Francesco Tedesco, 2016. "C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10346
    DOI: 10.1038/ncomms10346
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    Cited by:

    1. Fei Wang & Peiwen Ding & Xue Liang & Xiangning Ding & Camilla Blunk Brandt & Evelina Sjöstedt & Jiacheng Zhu & Saga Bolund & Lijing Zhang & Laura P. M. H. Rooij & Lihua Luo & Yanan Wei & Wandong Zhao , 2022. "Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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