Haematogenous dissemination of cells from human renal adenocarcinomas

Glaves, Dorothy; Huben, Robert P.; Weiss, Leonard

doi:10.1038/bjc.1988.4

Cited by 117 publications

(53 citation statements)

References 15 publications

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“…Two previous studies have reported on intraoperative sampling of effluent venous blood from colon and renal cancers, but neither determined whether surgery had any effect on the rate of cell shedding (Glaves et al, 1988;Leather et al, 1993). Preliminary results using a polymerase chain reaction (PCR) technique to detect circulating tumour cells were similar to our findings, although fewer patients were studied (Brown et al, 1994).…”

supporting

confidence: 80%

Induction of tumour cell shedding into effluent venous blood breast cancer surgery

Choy

McCulloch²

1996

Br J Cancer

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Summary Surgeons have long been concerned that cancer may be disseminated by shedding of tumour cells into the bloodstream during surgery. Early claims that cancer operations induced an increase in the number of tumour cells shed into the circulation were subsequently discredited, and the issue has remained unresolved. We used immunocytochemistry for cytokeratins to detect tumour cells in effluent blood from breast carcinomas in 18 patients undergoing surgery. Tumour cells were detectable in 6/18 patients during surgery, in only one patient before operation and in none post-operatively (P = 0.025). Circulating cells were associated with vascular invasion within the primary tumour (P = 0.032). No cytokeratin-positive cells were found in blood from ten normal volunteers or four patients undergoing surgery for other breast conditions. These results confirm that cancer surgery in humans results in an increase in the shedding of tumour cells into the circulation. The implications for prognosis and practice should be determined by larger prospective studies.Keywords: circulating cell; metastasis; surgery Blood-borne metastasis is the greatest obstacle to cure in patients with cancer. Metastasis is a complex process by which tumour cells enter blood vessels, circulate and exit the system at distant sites (Hart and Saini, 1992). Trauma to tumours increases both cell shedding and metastasis in animal models (Tyzzer, 1913;Liotta et al., 1976), leading to concern that cancer surgery might have similar effects in humans. Early studies of cell shedding in humans were confounded by major sampling and cell identification errors, and a general appreciation of the inadequacy of contemporary techniques led to a decline in interest in the subject (Salsbury, 1975). In recent years emphasis in metastasis research has shifted to the phenotype of the cancer cell, and a number of enzymatic and adhesion molecules have been implicated in the metastatic process (Fidler, 1991;Hart and Saini, 1992). The importance of the extent of tumour cell shedding into the bloodstream, and the effects of this on cancer surgery have, by contrast, been neglected. The significance of these factors in determining outcome therefore remains unknown.Monoclonal antibodies against epithelial-restricted epitopes now permit reliable identification of small numbers of carcinoma cells among large numbers of cells of haemopoetic lineage in the bloodstream and bone marrow (Leather et al., 1993;Pantel et al., 1993

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confidence: 80%

Induction of tumour cell shedding into effluent venous blood breast cancer surgery

Choy

McCulloch²

1996

Br J Cancer

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“…5,6 Many of these cells become nonviable and will not be able to complete the metastatic cascade and develop into a secondary tumor. 6,7 However, a small number of circulating cells complete the metastatic process. Our evidence suggests that the initial proliferation takes place within the blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Intravascular Location of Breast Cancer Cells after Spontaneous Metastasis to the Lung

Wong

Song

Grimes

et al. 2002

The American Journal of Pathology

115

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In this study, we examined the hypothesis that early pulmonary metastases form within the vasculature. We introduced primary tumors in immunocompromised mice by subcutaneous injection of murine breast carcinoma cells (4T1) expressing green fluorescent protein. Isolated ventilated and perfused lungs from these mice were examined at various times after tumor formation by fluorescent microscopy. The vasculature was visualized by counterstaining with 1,1-dioctadecyl-3,3,3 ,3 -tetramethylindocarbocyanine (DiI)-acetylated low-density lipoprotein. These experiments showed that metastatic cells derived by spontaneous metastases were intravascular, and that early colony formation was intravascular. The location of the tumor cells was confirmed by deconvolution analysis. This work extends our previous study 1 We recently reported direct observations of the sequence of events in pulmonary metastasis after injection of fluorescent tumor cells into the venous circulation using fluorescent microscopy of isolated perfused lungs. 1 Because endothelium has receptors for oxidized or acetylated low-density lipoprotein (LDL), the pulmonary endothelium can be precisely visualized in these preparations through infusion of DiI-acetylated LDL. Because the lung is translucent, these methods allow high-resolution imaging of the microvasculature of the lungs at up to 100-m depth beneath the pleural surface and enable the precise localization of the tumor cells. We used these methods to show in a mouse experimental metastasis model that tumor cells attach to the pulmonary endothelium and proliferate intravascularly.We have also demonstrated that differences in apoptosis of tumor cells in vivo correlated to differences in metastatic potential. 1-3 Based on these observations, we proposed a new model for pulmonary metastasis in which endothelium-attached tumor cells that survived the initial apoptotic stimuli proliferate intravascularly. A principal tenet of this new model is that extravasation of tumor cells is not a prerequisite for metastatic foci formation. [1][2][3] Because the initial experiments were based on intravenous injection of tumor cells, it was possible that the results were an artifact of this mode of introduction of the tumor cells or of the relatively large numbers of cells infused simultaneously. To determine whether our observations in an experimental model of metastasis were valid for cells that metastasize spontaneously from a primary tumor, we have tested our hypothesis using a spontaneous metastasis model. Our previous results were obtained using fibrosarcoma cells, so we sought to extend this hypothesis to carcinoma cells by using the breast carcinoma cell line 4T1. 4 The results indeed indicate that extravasation is also rare after spontaneous metastasis. These observations confirmed that metastasizing tumor cells proliferate intravascularly within the lung. This suggests that drug discovery efforts could be directed to blocking the metastatic cascade at the steps of the initial Supported by the Susan G. Komen Bre...

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“…Immunocytochemistry has demonstrated the presence of epithelial cells in the efferent blood of kidney (Glaves et al, 1988) and colonic tumours (Leather et al, 1993), and showed that surgical resection of breast tumours could induce the passage of epithelial cells into the distal venous blood circulation (Choy and McCulloch, 1996). This technique can demonstrate circulating epithelial cells beyond a density of 10 epithelial cells per ml of blood.…”

Section: Discussionmentioning

confidence: 99%

The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer

et al. 1999

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Transurethral resection of exophytic bladder tumours (TURT) is the first step in the management of bladder cancer. The procedure confirms the diagnosis and provides important prognostic information, including grading and staging of the disease. During endoscopy, the tumour and underlying muscle are resected. This procedure, performed under continuous irrigation, can lead to passage of the irrigating fluid, accompanied by benign and/or malignant epithelial cell suspensions, into the peripheral circulation, facilitated by inevitable venous breaches during resection, and by transient elevations of the intravesical pressure during resection (Hahn, 1995). Theoretically, this may contribute to disease progression, invasion and metastases as has been suggested in other malignancies, including breast and prostate cancer during open surgical excision which has been shown to induce passage of normal and malignant epithelial cells into the peripheral circulation (Eschwège et al, 1995;Choy and McCulloch, 1996; Oeflein et al, 1996). To our knowledge, however, haematogenous dissemination of epithelial cells during endoscopic resection of bladder cancer or during cystoprostatectomy has not been studied previously.The aim of our study was to evaluate prospectively the risk of haematogenous dissemination of epithelial cells following transurethral resection and cystoprostatectomy for bladder cancer. PATIENTS, MATERIALS AND METHODS PatientsThirty-three patients were studied. Two were thought to have malignant disease in the bladder, but were found to have non-specific inflammation (n = 1) and schistosomiasis (n = 1) with no evidence of malignancy. Thirty-one consecutive patients had different stages and grades of transitional cell carcinoma of the bladder, 25 of whom required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1), all tumours being single or multifocal with a total fresh weight less than 5 g, and no post-operative haemorrhagic complications; and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five of the remaining cancer patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1). The final patient who was analysed received a radical cystoprostatectomy 6 months earlier for a pT4G3 tumour, and developed pelvic recurrence and skeletal metastases. He was treated with systemic chemotherapy. Sample collection and preparationVenous blood samples (10 ml) were obtained by venepuncture from the antecubital fossa in every patient before surgery, and between 1 and 2 h after completion of the procedure. In the patient with known metastatic disease, blood samples were obtained prior to administration of chemotherapy. Summary This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had d...

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Haematogenous dissemination of cells from human renal adenocarcinomas

Cited by 117 publications

References 15 publications

Induction of tumour cell shedding into effluent venous blood breast cancer surgery

Induction of tumour cell shedding into effluent venous blood breast cancer surgery

Intravascular Location of Breast Cancer Cells after Spontaneous Metastasis to the Lung

The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer

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