Targeted destruction of androgen‐sensitive and ‐insensitive prostate cancer cells and xenografts through luteinizing hormone receptors

Leuschner, Carola; Enright, Frederick M.; Melrose, Patricia A.; Hansel, William

doi:10.1002/1097-0045(20010201)46:2<116::aid-pros1015>3.3.co;2-2

Cited by 6 publications

(25 citation statements)

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“…Although the LH/CG receptor capacity in MDA-MB-435S.luc cells was greater than LHRH receptor capacity (Table 1), the bCG-SPION uptake was lower than the LHRH-SPION accumulation. This observation could be explained by the difference in ligand receptor interaction, as the bCG ligand represents only a part (15 amino acids, 81-95 from the b chain of the CG ligand with the aminoacide sequence ''SYAVALSCQCALCRR'') of the ligand and facilitates the binding to the LH/CG receptors [38][39][40]46], whereas the LHRH decapeptide represents a complete ligand. The accumulation of these conjugated SPIONs in human breast cancer cells was highly efficient.…”

Section: Discussionmentioning

confidence: 99%

“…The homogenization buffer for membrane receptor assays was prepared as previously described [46]. Cells were grown to confluency, washed with sterile phosphate buffered saline (PBS), gently removed from the cell culture flask by scraping and collected in incubation media.…”

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

“…An aliquot of the cell suspension was used for determining the number of live cells by trypan blue staining. The cell membranes were prepared as previously described [46]. LH was radio-iodinated by the chloramine T method with 1.5 mCi of [ 125 I]-Na and the resulting iodinated LH was purified over PD10 columns.…”

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

“…LH was radio-iodinated by the chloramine T method with 1.5 mCi of [ 125 I]-Na and the resulting iodinated LH was purified over PD10 columns. The LH/CG assay was performed as previously described [46]. The binding was maximal for MDA-MB-435S and MDA-MB-435S.luc cells at 12 h and was stable until 18 h at 4°C.…”

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

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LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Leuschner

Kumar

Hansel

et al. 2006

Breast Cancer Res Treat

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159

114

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Targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) could facilitate their accumulation in metastatic cancer cells in peripheral tissues, lymph nodes and bones and enhance the sensitivity of magnetic resonance imaging (MRI). The specificities of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone/chorionic gonadotropin (LH/CG)- bound SPIONs were tested in human breast cancer cells in vitro and were found to be dependent on the receptor expression of the target cells, the time of incubation and showed saturation kinetics. In incubations with MDA-MB-435S.luc cells, the highest iron accumulation was 452.6 pg Fe/cell with LHRH-SPIONs, 203.6 pg Fe/cell with beta-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 degrees C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (betaCG or LHRH) decreased the iron accumulation in each case. LHRH-SPIONs were poorly incorporated by macrophages. Tumors and metastatic cells from breast cancer xenografts were targeted in vivo in a nude mouse model. LHRH-SPION specifically accumulated in cells of human breast cancer xenografts. The amount of LHRH-SPION in the lungs was directly dependent on the number of metastatic cells and amounted to 77.8 pg Fe/metastastic cell. In contrast, unconjugated SPIONs accumulated in the liver, showed poor affinity to the tumor, and were not detectable in metastatic lesions in the lungs. LHRH-SPION accumulated in the cytosolic compartment of the target cells and formed clusters. LHRH-SPIONs did not accumulate in livers of normal mice. In conclusion, LHRH conjugated SPIONs may serve as a contrast agent for MR imaging in vivo and increase the sensitivity for the detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs.

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Section: Discussionmentioning

confidence: 99%

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

Section: Radioreceptor Assays For Lh/cg and Lhrh Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Leuschner

Kumar

Hansel

et al. 2006

Breast Cancer Res Treat

Self Cite

159

114

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“…Despite a general prolonged survival rate by conventional chemotherapies that contain platinum, taxanes, and anthracyclines for ovarian cancer, there has been limited use of chemotherapy regimens due to significant side effects and a high recurrence rate. Cytostatics conjugated with hCG have significantly increased the toxicity in LHR-expressing breast (231) and prostate cancer cells (232,233). Treatment with hCG-conjugated doxorubicin for 2 h induced more than an 8-fold increase in cytotoxicity compared with unconjugated doxorubicin in ovarian cancer.…”

Section: Drug Developmentmentioning

confidence: 99%

Gonadotropins and Ovarian Cancer

et al. 2007

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Ovarian epithelial cancer (OEC) accounts for 90% of all ovarian cancers and is the leading cause of death from gynecological cancers in North America and Europe. Despite its clinical significance, the factors that regulate the development and progression of ovarian cancer are among the least understood of all major human malignancies. The two gonadotropins, FSH and LH, are key regulators of ovarian cell functions, and the potential role of gonadotropins in the pathogenesis of ovarian cancer is suggested. Ovarian carcinomas have been found to express specific receptors for gonadotropins. The presence of gonadotropins in ovarian tumor fluid suggests the importance of these factors in the transformation and progression of ovarian cancers as well as being prognostic indicators. Functionally, there is evidence showing a direct action of gonadotropins on ovarian tumor cell growth. This review summarizes the key findings and recent advances in our understanding of these peptide hormones in ovarian cancer development and progression and their role in potential future cancer therapy. We will first discuss the supporting evidence and controversies in the "gonadotropin theory" and the use of animal models for exploring the involvement of gonadotropins in the etiology of ovarian cancer. The role of gonadotropins in regulating the proliferation, survival, and metastasis of OEC is next summarized. Relevant data from ovarian surface epithelium, which is widely believed to be the precursor of OEC, are also described. Finally, we will discuss the clinical applications of gonadotropins in ovarian cancer and the recent progress in drug development.

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Targeted Ablation of Prostate Carcinoma Cells Through LH Receptor Using Hecate-CGβ Conjugate: Functional Characteristic and Molecular Mechanism of Cell Death Pathway

Bodek

Kowalczyk

Wacławik

et al. 2005

Exp Biol Med (Maywood)

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A Hecate-CGbeta conjugate (lytic peptide and beta-chorionic gonadotropin) selectively destroyed cells possessing LH receptors. This study described functional characteristics of the conjugate and the molecular mechanism of the cell death pathway in prostate cancer cells. Based on in vitro studies, we conclude that the conjugate kills cells possessing luteinizing hormone receptors (LHR) faster than Hecate alone. Competitive studies have shown that blocking of LHR by preincubation with chorionic gonadotropin (100 ng/ml) reduced toxicity of the conjugate in low concentrations. Further studies have also shown that the conjugate in treated cells both did not induce internucleosomal DNA fragmentation and did not induce morphological changes in cells characterized as having apoptotic features. These results proved that cells died by necrosis rather than apoptosis after the conjugate treatment.

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Targeted destruction of androgen‐sensitive and ‐insensitive prostate cancer cells and xenografts through luteinizing hormone receptors

Cited by 6 publications

References 0 publications

LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Gonadotropins and Ovarian Cancer

Targeted Ablation of Prostate Carcinoma Cells Through LH Receptor Using Hecate-CGβ Conjugate: Functional Characteristic and Molecular Mechanism of Cell Death Pathway

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