Summary
Parathyroid hormone-related protein (PTHrP), that has been identified as the main causative factor for the humoral hypercalcemia of malignancy, is nearly ubiquitiously expressed in tumours and normal tissues of various histogenesis. In normal tissues as well as in malignant conditions an auto- or paracrine function as growth and differentiation factor has been demonstrated. In cultured astrocytes of the rat brain we found an expression of the PTH/PTHrP receptor. Since normal astrocytes in situ and in vitro fail to express PTHrP by themselves, they presumably represent the physiological target for meningeal PTHrP via a paracrine mechanism. In normal astrocytes PTHrP induces an activation of adenyl cyclase accompanied by glial stellation, an effect possibly involved in the formation of the glial limiting membrane. Surprisingly, in the majority of the astrocytomas (grade II – grade IV, WHO-classification) PTHrP immunoreactivity can be detected. To test the biological significance of this observation we simultaneously performed the reverse transcription polymerase chain reaction for PTHrP and PTH/PTHrP receptor mRNA in three astrocytoma cell lines. In all three astrocytomas investigated the specific amplification products were detected, thus, indicating a possible autocrine function of PTHrP. In the monolayer proliferation assay the application of a monoclonal PTHrP-antibody against the receptor-binding N-terminus inhibited the proliferation of two astrocytoma cell lines, especially when they were seeded at low cell densities. Accordingly, in the clonogenic assay both cell lines showed a marked reduction in their ability to form clones. The data indicate a functional shift of PTHrP from a paracrine to an autocrine mode, occurring during the development of the astrocytomas. The simultaneous expression of PTHrP and its receptor and the effect on the proliferation in vitro substantiate its role as a growth factor in astrocytomas.
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© 1996 Birkhäuser Verlag Basel/Switzerland
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Turzynski, A., Struckhoff, G., Colangelo, D., Guidotto, S., Bunge, A., Dietel, M. (1996). Parathyroid hormone-related protein (PTHrP) — a paracrine factor in astrocytes and an autocrine factor in astrocytomas. In: Krisch, B., Mentlein, R. (eds) The Peptidergic Neuron. Advances in Life Sciences. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9010-6_38
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DOI: https://doi.org/10.1007/978-3-0348-9010-6_38
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