Human urinary bladder-carcinoma cells are non-osteoinductive

Abstract

Small pieces (ca. 2-3 x 3-5 mm) of the urinary-tract mucosa from noninvasive papillary transitional-cell carcinomas of the bladder (ca. urotheliale papillare, n = 33), invasive transitional-cell carcinomas of the bladder (ca. urotheliale papillare infiltrans, n = 6, papillary transitional-cell carcinomas of the bladder with squamous metaplasia (ca. urotheliale papillare cum metaplasia planoepitheliale, n = 4), transitional-cell carcinomas in situ (ca. urotheliale in situ, n = 2), and squamous-cell carcinomas of the bladder (ca. planoepitheliale, n = 2) were grafted intramuscularly into cortisone-immunosuppressed mice to test the ability of transformed transitional epithelium to induce heterotopic osteogenesis. Altogether, 156 implants from 47 cases of urinary bladder carcinoma were performed. Histological examination of implants, excised 10-17 days later, revealed relatively good survival of the grafted epithelium, which had proliferated and, in some cases, formed cysts and islands but failed to induce heterotopic osteogenesis in the surrounding host tissues. In nine implants prepared from four cases (noninvasive papillary transitional-cell carcinoma of the bladder and invasive papillary transitional-cell carcinoma of the bladder, two cases each) a small amount of cartilage and/or bone was found in the stroma of grafted tissue. The rarity of this phenomenon--together with the observation that implants of normal human urinary-tract mucosa have never induced the formation of cartilage/bone, whereas in a similar system, dog or guinea-pig grafts are osteogenic--suggests that the cartilage/bone present in the stroma of implanted cancers is the result of metaplasia of the stroma of the neoplasm and not the product of any osteoinductive potency of human urothelium.

Imaging and histopathological characteristics of carcinoma‐induced bone formation in skeletal muscle

“…15 There have been numerous studies demonstrating the ability of transplanted urinary bladder epithelium to induce bone formation in soft tissues. [15][16][17] This phenomenon has been studied and produces consistent results in dogs, cats, rabbits, gerbils and guinea pigs. 16 17 Histopathology in this patient demonstrated foci of immature woven bone lined by a single layer of plump well-differentiated osteoblasts.…”

“…The requirements of bone induction include the presence of osteogenic precursor cells (including mesenchymal cells distributed in normal tissues), the presence of inducing agents and an environment permitting osteogenesis such as muscle and fascia 15. There have been numerous studies demonstrating the ability of transplanted urinary bladder epithelium to induce bone formation in soft tissues 15–17. This phenomenon has been studied and produces consistent results in dogs, cats, rabbits, gerbils and guinea pigs 16 17.…”

“…Histopathology in this patient demonstrated foci of immature woven bone lined by a single layer of plump well‐differentiated osteoblasts. The presence of osteoblasts indicates that these cells likely induced true bone formation, resulting in the formation of an osseous metaplasia, compared with forming a stromal metaplasia which in human beings has been found to appear similar to the presence of hyaline cartilage or bone spicules but lacks osteoblast cell populations 17. In this patient, it could be hypothesised that heterogeneous metastasis of neoplastic urothelial cells occurred from an unknown primary location and stimulated bone induction as a result of the distant muscular and fascial tissues in which they were deposited.…”

Is Heterotopic Bone Formation, Occurring Near a Cut Ureter, a Sign of Osteoinductive Potency of Human Urothelium?

“…Only in 4 out of 47 cases of carcinoma urotheliale papillare examined was a small amount of calcifying carti lage, present in only a few serial sections, found. A detailed histological analysis of these 4 cases showed that the cartilage was present in the stroma of grafted tumor, rather than in the graft-surrounding area [21], Moreover, the pathologists did not report the presence of cartilage/ bone in the stroma of routine tumor biopsies. Thus, these cases should not be considered as an example of bone induction by human urothelium but merely as a stromal osseous metaplasia of the grafted tumor.…”