Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer

Kylmälä, Timo; Tammela, T.L.J.; Risteli, Leila; Risteli, Juha; Kontturi, M; Elomaa, Inkeri

doi:10.1038/bjc.1995.204

Cited by 86 publications

(59 citation statements)

References 22 publications

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“…Urinary collection is, moreover, often cumbersome in clinical practice. A serum-based assay measuring carboxyterminal type I collagen telopeptide (ICTP) has been developed and increased ICTP levels have been reported in prostate cancer patients with bone metastases (Kylmala et al, 1995;Yoshida et al, 1997;Akimoto et al, 1998). However, the tissue specificity and the clinical significance of serum ICTP levels are still unclear.…”

Section: Resultsmentioning

confidence: 99%

“…There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).…”

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confidence: 95%

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Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

217

128

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Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 95%

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

217

128

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“…However, tumor deposits in bone usually contain both bone formation and bone degradation (3)(4)(5)(6)(7)(8). A ''vicious cycle'' is created whereby metastatic tumor stimulates bone turnover and bone turnover promotes local tumor growth.…”

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confidence: 99%

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

Cher

Biliran

Bhagat

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

147

150

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Emerging evidence indicates that tumor-associated proteolytic remodeling of bone matrix may underlie the capacity of tumor cells to colonize and survive in the bone microenvironment. Of particular importance, urokinase-type plasminogen activator (uPA) has been shown to correlate with human prostate cancer (PC) metastasis. The importance of this protease may be related to its ability to initiate a proteolytic cascade, leading to the activation of multiple proteases and growth factors. Previously, we showed that maspin, a serine protease inhibitor, specifically inhibits PC-associated uPA and PC cell invasion and motility in vitro. In this article, we showed that maspin-expressing transfectant cells derived from PC cell line DU145 were inhibited in in vitro extracellular matrix and collagen degradation assays. To test the effect of tumor-associated maspin on PC-induced bone matrix remodeling and tumor growth, we injected the maspin-transfected DU145 cells into human fetal bone fragments, which were previously implanted in immunodeficient mice. These studies showed that maspin expression decreased tumor growth, reduced osteolysis, and decreased angiogenesis. Furthermore, the maspin-expressing tumors contained significant fibrosis and collagen staining, and exhibited a more glandular organization. These data represent evidence that maspin inhibits PC-induced bone matrix remodeling and induces PC glandular redifferentiation. These results support our current working hypothesis that maspin exerts its tumor suppressive role, at least in part, by blocking the pericellular uPA system and suggest that maspin may offer an opportunity to improve therapeutic intervention of bone metastasis.A ndrogen deprivation therapy has been the mainstay of treatment of metastatic prostate cancer (PC) for Ͼ50 years. Usually, this therapy produces tremendous tumor shrinkage and significant clinical improvement. However, the duration of response is limited and disease always recurs. Cytotoxic chemotherapy is commonly added, although this approach offers little chance for meaningful, long-term survival. Thus, new approaches are needed. The skeleton is the major target organ of metastasis in patients with PC, and bone metastasis is associated with poor survival. Can bone-targeted therapy improve survival? In a recent clinical trial (1), a therapeutic, bone-seeking radioisotope was added to standard chemotherapy in patients showing an initial chemotherapeutic response. Survival was prolonged in the patients receiving the bone-seeking radioisotope compared with those receiving chemotherapy alone, suggesting that targeting skeletal metastases is a promising approach in PC treatment.Clinicians have traditionally classified bone metastases as either osteolytic or osteoblastic (2). However, tumor deposits in bone usually contain both bone formation and bone degradation (3-8). A ''vicious cycle'' is created whereby metastatic tumor stimulates bone turnover and bone turnover promotes local tumor growth. To date, various molecules have been implicated ...

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“…The levels of these markers in cyst fluid very probably reflect matrix reactions within the tumour; in peritoneal/ascitic fluid their levels may be consequent to tumourinduced reactions within the peritoneal cavity, whereas those observed in the serum may originate from the tumour, from the peritoneal cavity, from the reactions of the host to ovarian neoplasm or from all of these. In the interpretation of the results, we have put a special emphasis on (a) parallel investigation of synthesis and breakdown of type I collagen; (b) parallel evaluation monitoring their response to therapy (Kylmala et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer

Santala

Risteli²,

Risteli³

et al. 1998

Br J Cancer

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Summary The synthesis and degradation of type I and type IlIl interstitial collagens releases several antigenic metabolites, whose measurement allows the metabolism of connective tissue to be evaluated under a variety of different conditions. In this study we investigated the influence of benign and malignant ovarian neoplasms on the metabolism of these collagens. The study population comprised patients with benign (n = 53), borderline (n = 6) or malignant (n = 36) ovarian neoplasms. We quantified the serum, cyst fluid and peritoneal/ascitic fluid concentrations of the amino-terminal propeptide of type (PINP) and IlIl (PIIINP) procollagens, indicators of the synthesis of type and IlIl collagen, respectively and the cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), ani indicator of type I collagen degradation.Macrophage colony-stimulating factor 1 (CSF-1) concentration was also assayed as its serum level is increased in ovarian cancer and CSF-1 may be involved in the regulation of collagen metabolism. The concentration of each antigen was significantly higher in patients with malignant tumour than with benign neoplasm in each comparison, except for ICTP in peritoneal fluid and for CSF-1 in cyst fluid. The high ascitic fluid concentration of PINP, PIIINP or CSF-1 correlated with malignancy, and the low cyst fluid concentration of any of the four markers was indicative of benign tumour. Levels of CSF-1 did not correlate with the levels of any of the markers of collagen turnover. The concentration of PINP in ascites was about 50 times higher and in cyst fluid about eight times higher than that in the serum from patients with malignant tumour, whereas the respective ratios for ICTP were only 2.5 and 1.3. In such patients, the ratio of ascitic fluid to serum concentration was also about 80-fold higher for PIIINP and about 20-fold higher for PINP than for ICTP. The different distributions of PIIINP, PINP and ICTP suggests dominance of synthetic processes or retarted elimination of PIIINP and PINP in ovarian cancer. In advanced malignancies, the accumulation of PINP and PIIINP in abdominal space, possibly due to increased synthesis and/or failed resorption, may promote ascites formation. This study shows that both accelerated synthesis and breakdown of fibrillar collagens are characteristic of ovarian malignancy, and suggests that measurements of cyst fluid or ascitic fluid concentrations of collagen metabolites or CSF-1 could be used in the differential diagnosis of benign and malignant ovarian neoplasms.Keywords: matrix reaction; type collagen; type IlIl collagen; macrophage colony-stimulating factor 1; tumour-associated marker; ascites formationThe growth and dissemination of malignant neoplasms are accompanied by complex biochemical events that alter collagen metabolism. During tumour growth and dissemination the increased synthesis of proteolytic enzymes with the consequent disruption of collagen architecture is a prerequisite for neoplastic cell invasion and dissemination (Liotta, 1986; van den ...

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Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer

Cited by 86 publications

References 22 publications

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer

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