Tumor‐associated fibroblasts recruit blood monocytes into tumor tissue

T Silzle, M Kreutz, MA Dobler… - European journal of …, 2003 - Wiley Online Library
T Silzle, M Kreutz, MA Dobler, G Brockhoff, R Knuechel, LA Kunz‐Schughart
European journal of immunology, 2003Wiley Online Library
Tumor‐associated fibroblasts (TAF) and tumor‐associated macrophages are the main
stromal components in desmoplastic breast tumors. These host cell types were extensively
studied individually with regard to tumor development and progression but little is known
about their reciprocal interactions. To elucidate the role of TAF in the recruitment of
monocytes (MO) we designed a 3D co‐culturesystem of multicellular fibroblast spheroids of
different origin, co‐cultured with MO suspensions from healthy donors. Spheroids of tumor …
Abstract
Tumor‐associated fibroblasts (TAF) and tumor‐associated macrophages are the main stromal components in desmoplastic breast tumors. These host cell types were extensively studied individually with regard to tumor development and progression but little is known about their reciprocal interactions. To elucidate the role of TAF in the recruitment of monocytes (MO) we designed a 3D co‐culturesystem of multicellular fibroblast spheroids of different origin, co‐cultured with MO suspensions from healthy donors. Spheroids of tumor‐derived but not of normal fibroblasts were extensively infiltrated by MO. A linear correlation between number of infiltrated MO and number of MO applied per spheroid was shown, indicating a distinct migratory MO subpopulation (≈15%) within the peripheral blood MO pool. Our data imply that MO migration into fibroblastic tumor areas may partially result from high expression of CCL2 (monocyte chemotactic protein‐1), which was regulated by endogenousIL‐6 as shown by neutralization experiments. The effect of CCL2 on MO migration was inhibited by CCL2 neutralizing antibody in tumor‐derived fibroblast conditioned media in a Boyden chamber migration assay but not in spheroid culture. While this phenomenon needs further evaluation, our data clearly support the concept of fibroblasts as "sentinel cells" relevant for tumor progression.
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