Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer

To elucidate the role of tumor-associated macrophage (TAM) in the loss of ERα in endometrial cancer (EC) and the underlying mechanism.

Tissue microarrays and immunohistochemistry assays were performed using endometrial cancer tissue along with coculture, immunofluorescence, invasion assays and ChIP-qPCR using a human endometrial cancer cell line.

Compared with normal tissue, an increased number of TAM was found in EC tissue (34.0 ± 2.6 vs. 8.3 ± 1.1, respectively; p < 0.001), which may downregulate ERα (27.4%, p < 0.05 for HEC-1A and 16.9%, p < 0.05 for Ishikawa) and promote EC cell invasion (1.8-fold, p < 0.001 for HEC-1A and 2.0-fold, p < 0.001 for Ishikawa). Furthermore, we found that TAM-derived CXCL8 mediated the loss of ERα and cancer invasion via HOXB13. HOXB13 was highly expressed in the ERα-negative subtype (r = -0.204, p = 0.002) and low expression of ESR1 was associated with a poor prognosis for EC patients (log-rank p < 0.05).

TAM-secreted CXCL8 downregulated the ERα expression of EC cells via HOXB13, which may be associated with cancer invasion, metastasis and poor prognosis.