Tumor-associated
inflammation has been linked to angiogenesis,
metastasis and poor prognosis. The 18 kDa translocator
protein (TSPO), also known as the peripheral
benzodiazepine receptor (PBR), is expressed in activated immune cells such as macrophages, but also in a number of
cancer cell lines such as those of
breast cancer. There is an increasing clinical interest in TSPO expression as it has been proposed as a poor prognostic factor for survival in lymph-node negative
breast cancer patients. This study aims to assess of the presence of neoplastic cell-associated TSPO and
tumor macrophage-associated TSPO in mouse xenografts generated from the MDA-MB-231 and the MCF-7
breast cancer cell lines, as well as 25 different
breast tumors originally derived from patient-tissue but propagated in mice using two
antibodies, each specific to either the human or the murine form of TSPO. Autoradiography with the TSPO
ligand [¹⁸F]
DPA-714 and immunohistochemistry were also performed on the excised
tumor tissues from the MDA-MB-231, MCF-7 and one of the patient-derived xenografts (HBCx-12B). High TSPO expression (either
cancer or stromal cell-associated, or both) was measured in 20/25 (80%) of the patient-derived
breast cancer xenografts. [¹⁸F]
DPA-714 showed displaceable binding to both the human and murine TSPO on
tumor tissue sections. Immunohistochemistry demonstrated that a significant portion of the
tumor stromal TSPO expression colocalized with F4/80 positive macrophages cells. This study constitutes a first report of the
tumor TSPO expression by mixed cell populations, and it may have important implications for
cancer biology as well as for the development of imaging and therapeutic
ligands targeted to TSPO.