In Vitro and In Vivo Expression of Opioid and σ Receptors in Rat C6 Glioma and Mouse N18TG2 Neuroblastoma Cells

Abstract

Mouse N18TG2 neuroblastoma and rat C6 glioma cell lines were injected into male nude mice, and the tumors were passaged serially. At each generation, tumors were analyzed for δ opioid binding using [3H][d‐Ala2,d‐Leu5]enkephalin and for σ1 and σ2 binding with 1,3‐[3H]di‐o‐tolylguanidine in the presence and absence of 1 µM pentazocine. Receptor density (Bmax) and affinity (KD) were estimated by homologous competition binding assays. Opioid and σBmax values in the solid tumors were significantly lower than their original levels in vitro. KD values for opioid/σ ligands were similar in vitro and in vivo. With successive passages in the murine host, δ opioid and σ1 binding of the neuroblastoma‐derived solid tumors became undetectable. In contrast, σ2 receptor Bmax values were unchanged with successive passages of the neuroblastoma‐derived tumors and doubled in the nude mouse‐borne gliomas. When neuroblastoma‐derived solid tumors that were devoid of δ opioid binding were returned to culture, opioid receptors appeared to be up‐regulated as compared with their original in vitro levels. Serial passaging of these recultured cells in vivo again resulted in a rapid decline in opioid receptor content. The opioid data are consistent with our prior findings on opioid binding diminution in human brain tumors. The pattern of change for σ binding was more complex, with the σ2 response in late passages of the glioma being reminiscent of the formerly observed increase in number of σ sites in transformed human meninges, kidney, and colon tissue.

Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy

“…Sigma-2 receptor expression has been reported in various human cancer cells such as breast[19], brain[20], bladder[21], colon and melanoma[22]; however, no studies have been reported on sigma-2 receptor expression in pancreas adenocarcinoma. Sigma-2 receptor-specific ligands have been found to induce apoptosis [19-22], raising the possibility that these ligands can act as sensitizers to standard chemotherapies.…”

The Targeted SMAC Mimetic SW IV-134 is a strong enhancer of standard chemotherapy in pancreatic cancer

“…Sigma-2 receptors are up-regulated in many cancer types [39, 40] and SMAC mimetics have been shown to sensitize many types of cancer to a wide array of chemotherapeutic agents [17, 41, 42]. As a result, we believe that SW IV-134 could potentially be used to sensitize several additional sigma-2-expressing malignancies, including head and neck tumors, breast cancer, lymphomas [43], and ovarian cancer [22] to different chemotherapeutics.…”

Imaging Sigma Receptors: Applications in Drug Development

“…For the sigma-1 receptor specifically, as examples these include cancers of the breast (except MCF-7 cells), lung (small cell and non-small cell lung cancer cells), colon, ovaries and prostate (androgen dependent and androgen independent cancers) and brain [28,118,[302][303][304][305][306][307][308] . The reported Bmax range for these cancer cell lines is 180 -6839 fmol/mg protein (most are well above 1000 fmol/mg protein), including those of rodent and human origin.…”