Patterns and Mechanisms of Localized Bone Invasion by Tumors: Studies with Squamous Carcinomas of the Head and Neck

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Abstract
Squamous carcinomas of the head and neck provide a useful model for analyzing patterns and mechanisms of tumor-associated bone destruction. Morphological studies show that a major part of the invasive process is mediated by local osteoclasts which erode bone in front of the advancing tumor. Functional studies indicate that both fresh tumors and tumor cell lines resorb calvarial bone in an in vitro test system, again by stimulating local osteoclasts. Prostaglandins of the E2 type are regularly released by the tumors, together with indomethacin-resistant, nonprostaglandin osteolysins. Control (nonneoplastic) tissues will resorb bone and release osteolytic factors, usually at lower levels of activity--such properties are thus tumor-associated rather than tumor-specific. Xenografts of squamous carcinomas resorb bone in vitro and synthesize osteolysins. They do not invade local bone in their hosts but some grafts regularly produce a systemic hypercalcemia. General implications are discussed, particularly for other human tumors which more frequently metastasize to bone. Possible pointers to the (partial) control of the destructive process are noted.