Knochenmetastasen

Zusammenfassung

Knochenmetastasen sind ein klinisch relevantes Problem und ihre Inzidenz nimmt zu. Die Fähigkeit von Tumorzellen, in den Knochen zu metastasieren, erfordert zellbiologische Veränderungen, die zur Migration und zur aktiven Überwindung von Barrieren wie Basalmembranen und Extrazellulärmatrix befähigen. Das „Homing” im Knochen findet dann statt, wenn Tumorzellen dort anheften und gut überleben können. Die Interaktion der beteiligten Zelltypen bewirkt eine Änderung des Phänotyps in allen Partnern einer solchen „malignen Konversation”. Die resultierende Signatur ist oft permanent und führt auf der einen Seite zu einer Suszeptibilität des Stromas für die Metastasierung und auf der anderen Seite zu einer starken Veränderung der Tumorbiologie, die sich vom Primärtumor wesentlich unterscheidet. In einem klassischen Circulus vitiosus können Tumorzellen direkt und indirekt Osteoklasten stimulieren und Osteolysen verursachen. Auf die Osteoblastenfunktion können sie zweierlei Auswirkungen haben. Sie können die Mineralisierung stark stimulieren und damit osteoblastische Metastasen verursachen, sie können aber auch starke Hemmstoffe der Knochenregeneration ausschütten, die eine Osteoplegie hervorrufen, ein völliges Lahm legen der Knochenregeneration. Die Kombination aus Osteolyse und Osteoplegie führt klinisch zu einer besonders schwerwiegenden Situation des Knochenverlusts mit pathologischen Frakturen. Die geschützten Stammzellnischen des Knochenmarks sind auch für Tumorzellen eine gute Möglichkeit zum Überleben. Tumorzellen können sich diese Nischen selbst induzieren. Sie können sich dabei in Richtung Tumorstammzelle verändern und können später zum Ausgangspunkt von Tumorrezidiven werden. Es ist daher für die Zukunft sinnvoll, den Knochen und das Knochenmark als therapeutische Zielstrukturen in onkologische Therapiekonzepte einzubeziehen.

Summary

Bone metastases are an important clinical problem and their incidence is increasing. In order to metastasize to bone tumour cells have to undergo changes that facilitate migration and active crossing of basal membranes and extracellular matrix. Tumour cells home to bone if they find suitable adherence and survival conditions. Interaction between the various cell types involved induces changes in the cellular phenotype of all partners of such „malignant conversation”. The resultant signature is often permanent and leads to both increased susceptibility for metastasis in stromal cells and to fundamental biological changes in tumour cells which at the end are markedly different from primary tumour biology. In a classical vicious cycle tumour cells directly and indirectly stimulate osteoclasts to resorb bone, thereby causing bone loss and osteolysis. Tumour cells can influence osteoblast activity in that they overstimulate mineralization activity, which leads to osteoblastic metastases, or they completely inhibit bone regeneration which may be addressed as „osteoplegic” metastases. The combination of osteolytic and osteoplegic activity of tumour cells causes detrimental bone loss and pathological fractures. Protected niches of the bone marrow provide excellent survival conditions for tumour cells. They are able to induce niches on osteogenic cells in order to develop attitudes of tumour stem cells, which render them a source of secondary tumour relapse. Bone and the bone marrow provide important and promising targets that should be incorporated into future anti-tumour strategies.

Schlüsselwörter

Tumorzellen - Knochenmetastasen - Stammzellnischen - Tumorrezidiv

Keywords

Tumour cells - bone metastases - stem cell niche - secondary tumour relapse

^* http://www.skelmet.de

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