Individual development and uPA–receptor expression of disseminated tumour cells in bone marrow: A reference to early systemic disease in solid cancer

Abstract

It is unclear whether disseminated tumour cells detected in bone marrow in early stages of solid cancers indicate a subclinical systemic disease component determining the patient's fate or simply represent mainly irrelevant shed cells. Moreover, characteristics differentiating high and low metastatic potential of disseminated tumour cells are not defined. We performed repeated serial bone marrow biopsies during follow-up in operated gastric cancer patients. Most patients with later tumour relapse revealed either an increase or a constantly high number of tumour cells. In contrast, in patients without recurrence, either clearance of tumour cells or negative or low cell counts were seen. Urokinase plasminogen activator (uPA)-receptor expression on disseminated tumour cells was significantly correlated with increasing tumour cell counts and clinical prognosis. These results demonstrate a systemic component in early solid cancer, indicated by early systemically disseminated tumour cells, which may predict individual disease development.

MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients

“…Currently much effort is ongoing to characterize epithelial cells in bone marrow [11][12][13][14] and the expression of the urokinase plasminogen activator (uPA)-receptor on disseminated CK18-positive cells was found to correlate with poor prognosis in curatively resected gastric cancer patients. 15 The present study demonstrates a positive association between the negative MHC class I phenotype of disseminated tumor cells in bone marrow and an unfavorable outcome in breast cancer patients with minimal residual disease, suggesting that MHC class I downregulation is a prerequisite for the development of bone metastasis.…”

Immunotherapy of malignant ascites with trifunctional antibodies

“…Its use in earlier stages of peritoneal carcinomatosis after surgical peritonectomy or as adjuvant treatment in patients with high risk for developing of peritoneal carcinomatosis 11 or minimal-residual tumor disease 36 will outline the potential therapeutic impact of trifunctional antibodies.…”

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

“…Thus it is one of the molecules promoting invasion and metastasis that has repeatedly been shown to be predictive of a poor clinical prognosis of diverse carcinomas (Janicke et al, 1993;Ganesh et al, 1994;Nekarda et al, 1994;Heiss et al, 1995). In cancer, a high expression of u-PAR is mainly brought about at the transcriptional level, although other mechanisms at the post-transcriptional level may be involved (Wang et al, 1994;Shetty et al, 1997).…”