American Association for Cancer Research
Browse
10780432ccr191268-sup-220425_2_supp_5676137_pvdvkw.pdf (135.98 kB)

Figure S1 from Metastatic Breast Carcinoma–Associated Fibroblasts Have Enhanced Protumorigenic Properties Related to Increased IGF2 Expression

Download (135.98 kB)
journal contribution
posted on 2023-03-31, 21:06 authored by Yirui Gui, Adriana Aguilar-Mahecha, Urszula Krzemien, Abdel Hosein, Marguerite Buchanan, Josiane Lafleur, Michael Pollak, Cristiano Ferrario, Mark Basik

Figure S1 shows the immunophenotype of CAFs

Funding

Canadian Cancer Society

FRQS

History

ARTICLE ABSTRACT

The microenvironment of metastatic breast cancer is incompletely characterized, despite prior evidence that it plays a key role in the biology of metastasis. A major component of the tumor stroma is the carcinoma-associated fibroblast (CAF), which has been shown to communicate with other stromal and cancer cells to create a protumorigenic milieu. Our study was designed to characterize human CAFs from different metastatic sites. We collected eight carcinoma-associated fibroblasts (mCAFs) from different metastatic sites and compared them with CAFs from primary tumors (pCAFs) and with normal breast fibroblasts (NFs). Molecular profiles and effects on breast cancer cell growth, on response to doxorubicin and on T-cell proliferation were compared. We observed marked differences in mCAFs compared with pCAFs and NFs with respect to in vitro proliferation and effects on breast cancer cell migration, spheroid growth, invasion, response to doxorubicin, and in vivo tumor growth. We found marked transcriptomic differences between mCAFs and pCAFs, including increased expression of IFN-related genes and IGF2 in the former. Cluster analysis revealed two groups of mCAFs, with the liver mCAFs clustering together, with increased PDGFA expression. Treatment with an antibody against insulin-like growth factors (BI836845) inhibited growth of mixed mCAF-tumor cell xenografts in vivo. Also, mCAFs had a suppressive effect on T-cell proliferation. This is the first comparative analysis of a set of CAFs from metastatic sites in breast cancer. It revealed a marked protumorigenic effect in these mCAFs, which occurs in part through increased expression of IGF2.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC