Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes

Lin, Wen-chang; O’Connor, Kathleen L.; Culp, Lloyd A.

doi:10.1038/bjc.1993.170

Cited by 12 publications

(4 citation statements)

References 28 publications

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“…These development pat- Figure 6c). In contrast, most of the LZPt-3 cells in a 2-week-old tumour persisted in their round morphology (Figure 6d) (Lin et al, 1990a(Lin et al, , 1993 (Hagiwara et al, 1993). Overall, these studies reveal many similarities and only a few subtle differences in the tumour progression characteristics among N-type, S-type (or Schwannian-type cells;Sugimoto et al, 1988) spreading in situ, compared with their spreading into N-, Sand I-type cells in culture (Rettig et al, 1987;Ciccarone et al, 1989), provides further evidence for the distinctive tumour cell-matrix adhesion mechanisms operating in host tissues .…”

Section: Methodsmentioning

confidence: 99%

“…Alternative histochemical marker genes -Drosophila alcohol dehydrogenase or human placental alkaline phosphatasewere also developed to genetically tag two or more tumour cell classes to evaluate metastatic co-routing in virtually any host tissue . Co-injection of ras-or sistransformed fibroblasts, tagged with different histochemical marker genes, demonstrated intercellular cooperation during the earliest events in experimental metastasis by two closely related tumour cell derivatives (Lin et al, 1992(Lin et al, , 1993, as well as insight into some aspects of tumour cell clearance in target organs (Lin et al, 1990b;Lin & Culp, 1992a). The lacZ marker gene has now been used to tag breast carcinoma cells (Brunner et al, 1992), melanoma cells (Dooley et al, 1993) and glioblastoma cells (Lampson et al, 1993), as well as to track therapeutic 'targeting' genes to tumour cell populations in situ (Vile & Hart, 1993).…”

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confidence: 99%

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Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

Kleinman

Lewandowska²,

Culp³

1994

Br J Cancer

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

Kleinman

Lewandowska²,

Culp³

1994

Br J Cancer

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“…CD44 expression was inversely correlated, however, with N-myc oncogene amplification in neuroblastoma [10]. A mouse fibrosarcoma model system has been developed in our laboratory and characterized extensively for tumor progression in nude mice in vivo [15][16][17][18][19][20]. It consists of Balb/c 3T3 (clone A31) cells and its derivatives transformed with v-Ki-ras (Ki-3T3 cells), human EJ-Ha-ras (LZEJ or LZEJ-7 cells), or human c-sis (APSI or HUSI cells) oncogenes and in some cases co-transfected with histochemical marker genes to facilitate early detection of micrometastases.…”

Section: Introductionmentioning

confidence: 99%

“…C-sis transformants are tumorigenic but do not form metastases after subcutaneous injection (spontaneous metastasis assay), although they display lung colonization following intravenous injection of tumor cells (experimental metastasis assay) [ 17]. A number of cell lines have been established from first-and secondround primary tumors, as well as metastases, of these ras transformants.…”

Section: Introductionmentioning

confidence: 99%

Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with metastatic competence

Kogerman

Culp

1996

Clin Exp Metast

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Oncogene-dependent regulation and tumor relatedness of CD44 expression were investigated in Balb/c 3T3 cells and their derivatives transformed with different ras oncogenes (metastatic tumor model) or the human c-sis oncogene (non-metastatic model). Ras transformants using either the Harvey or Kirsten oncogenes expressed high levels of cell surface CD44 protein that bound fluoresceinated hyaluronan (HA). Much lower levels of CD44 were expressed in parental 3T3 cells, ras- revertants generated from Kirsten-transformed cells, or c-sis transformants, confirming the significance of the ras oncogene in this upregulation. To determine whether endogenous HA regulates these parameters, hyaluronidase treatment of ras transformants exposed more cell surface CD44 to anti-CD44 antibody and increased fluoresceinated HA binding; this did not occur with 3T3 or c-sis transformants. CD44 expression and its HA-binding function were conserved in a panel of in vivo primary and lung metastatic tumor cell lines derived from ras transformants. Ras transformants also retained the ability to downregulate CD44 protein levels in confluent cultures which occurred through a translational or post-translational mechanism (as CD44 mRNA levels were not reduced). These results taken together demonstrate that ras-dependent regulation of CD44 may correlate with tumor progression and metastasis in vivo, possibly (although not exclusively) supporting CD44's importance in metastatic progression.

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CD44 protein levels and its biological activity are regulated in Balb/c 3T3 fibroblasts by serum factors and by transformation with theras but not with thesis Oncogene

Kogerman

Culp

1996

J. Cell. Physiol.

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CD44s (standard isoform) levels and hyaluronan-binding activity were investigated in Balb/c 3T3 cells and their derivatives transformed with ras or sis oncogenes as a function of serum concentration in the medium. 3T3 cells contained low levels of CD44 and did not bind hyaluronan when grown in medium containing 0.5 or 10% serum. In 5% serum, however, the cells had much higher levels of CD44 and were able to bind hyaluronan. CD44 levels also increased in 3T3 cells restimulated with either 5 or 10% serum after prior maintenance in low serum. In cells restimulated with 5% serum, high levels of CD44 were sustained for at least 72 hr. In cells restimulated with 10% serum, however, the increase in CD44 levels reverted by 48 hr. Transformation of 3T3 cells with ras (but not with sis) oncogene rendered CD44 levels insensitive to serum modulation: ras-transformed cells contained high levels of CD44 and bound hyaluronan at all serum concentrations and at all time points tested. Sis-transformed cells behaved like 3T3 cells in these modulatory changes. Platelet-derived growth factor (PDGF), when supplementing 0.5% serum, mimicked the effects of serum on the levels and hyaluronan-binding capacity of CD44 in 3T3 cells and the CD44-upregulating activity of serum was neutralized by incubation with anti-PDGF antibodies. These data demonstrate that serum factors, specifically PDGF, mediate regulation of CD44 levels in BAlb/c 3T3 cells and that transformation of 3T3 cells by ras renders CD44 expression insensitive to the modulating effects of serum in vitro. These results correlate with the metastatic capacity of these cells in vivo.

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Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes

Abstract: The ras oncogene conveys some metastatic competence to tumour cells in a large number of biological systems (Bar-

Cited by 12 publications

References 28 publications

Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with metastatic competence

CD44 protein levels and its biological activity are regulated in Balb/c 3T3 fibroblasts by serum factors and by transformation with theras but not with thesis Oncogene

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