Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites

Nicolson, Garth L.

doi:10.1016/0304-419x(88)90010-8

Cited by 243 publications

(207 citation statements)

References 206 publications

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“…The metastatic process is a series of sequential steps in which tumor cells are released from the primary tumor and disseminated to distant sites, where they proliferate to form new tumor foci [1,2]. Dynamic cell movement observed in tumor metastasis is similar to that observed during embryonic morphogenesis, although there is a difference that tumor cells move, destroying normal tissues, whereas normal cells move, maintaining homeostasis in morphogenesis.…”

Section: Introductionmentioning

confidence: 96%

HOXD3-overexpression increases integrin αvβ3 expression and deprives E-cadherin while it enhances cell motility in A549 cells

Ohta

Hamada

Tada

et al. 2006

Clin Exp Metastasis

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We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin β3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin β3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays.The integrin β3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin αv subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin β3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin β3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin β3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin αv β3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.

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Section: Introductionmentioning

confidence: 96%

HOXD3-overexpression increases integrin αvβ3 expression and deprives E-cadherin while it enhances cell motility in A549 cells

Ohta

Hamada

Tada

et al. 2006

Clin Exp Metastasis

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“…Although significant progress has been made in the last decade for early detection of tumours and treatment of clinically less advanced carcinoma, management of advanced breast cancer has still not improved. The process of metastasis is complex: it involves cascades of various biochemical and molecular steps (Liotta et al, 1983;Nicolson, 1988). Factors associated with both the host tissue and the malignant cells play crucial roles in the invasion and metastasis of tumour cells (Boghaert et al, 1992;Lester and McCarthy, 1992).…”

Section: Discussionmentioning

confidence: 99%

Development of a new metastatic human breast carcinoma xenograft line

Mehta

Graves²,

Shilkaitis³

et al. 1998

Br J Cancer

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Summary Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient's tumour from which the xenograft line originated. Both the xenograft and the patient's tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogenresponsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.Keywords: breast cancer; xenograft; cell line; metastasis Metastasis of primary tumour to the visceral organs is a major cause of cancer-associated mortality. Despite considerable progress in the last decade in the areas of early detection and surgical and chemotherapeutic management of clinically less advanced cancers, treatment of metastatic disease is still a major puzzle for oncologists. Research on metastatic disease has severely suffered from lack of suitable experimental models. Human tumour xenografts established from well-characterized clinical material provide an important research tool for multidisciplinary research. In most cases, xenografts originated in vivo in experimental animals preserve many of the original phenotypic, biological and genotypic characteristics from which they originate (Giovanella et al, 1989;Mehta et al, 1995a). However, human breast carcinomas are difficult to grow in vitro in culture (Nordquist et al, 1975;Engel and Young, 1978;Langlois et al, 1979;Whitehead et al, 1983;Chu et al, 1985;Mehta et al, 1992;1995b ;Watanabe et al, 1992) or in vivo in experimental animals (Sabestany et al, 1979;Shafie and Liotta, 1980;Rae-Venter and Reid, 1980;Giovanella et al, 1985;Price and Zhang, 1990;Hurst J, et al, 1993; Mehta et al, 1993), and they rarely metastasize when transplanted subcutaneously (Shafie and Liotta, 1980;Price et al, 1990; Brunner et al, 1992; Mehta et al, 1993).Recently, we obtained significant success in establishing xenografts from primary breast carcinomas, and many of these xenografts showed potential for spontaneous metastasis in athymic mice when transplanted s.c. (Mehta et al, 1993). Initially, we used Matrigel to develop xenografts from primary breast carci...

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“…The process of metastasis has been considered to be a complex phenomenon developing late in tumour progression where accumulation of somatic mutations, coupled with strong environmental selection pressures, has led to the emergence of more aggressive clonal subpopulations (Nowell, 1976). Regulation of the process has been presumed to result from the activation/repression of a number of specific genes (Nicolson, 1988 (Bradley et al, 1986;Egan et al, 1987a,b;Greig et al, 1985).…”

Section: Transfection Studiesmentioning

confidence: 99%