Further Observations on the Occurrence of Nexuses in Benign and Malignant Human Cervical Epithelium

McNutt, N. Scott; Hershberg, Robert A.; Weinstein, Ronald S.

doi:10.1083/jcb.51.3.805

Cited by 126 publications

(30 citation statements)

References 85 publications

(151 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may appear that our findings conflict with evidence that numbers of gap junctions in suprabasal cervical epithelium are decreased at an early stage of dysplasia, possibly to the low numbers normally seen in the basal layer (McNutt et al, 1971;King et al, 2000b). However, this could simply reflect a failure of the increased connexin expression normally associated with differentiation, the small numbers of junctions remaining being sufficient for metabolic cooperation.…”

Section: Gjic-proficient Hela Cells Stably Transfected With Cx43contrasting

confidence: 56%

See 1 more Smart Citation

The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression

et al. 2003

View full text Add to dashboard Cite

Disruption of gap junctional intercellular communication (GJIC) and/or connexins (gap junction proteins) is frequently reported in malignant cell lines and tumours. Certain human papillomaviruses (HPV) associated with the development of cancers, especially of the cervix, have previously been reported to downregulate GJIC in vitro. There is also evidence for reduced gap junctions in cervical dysplasia. However, many squamous hyperproliferative conditions, including HPV-induced warts, often show extensive upregulation of certain connexins. The association between HPV and GJIC, and the mechanism and consequence of deregulated GJIC in cervical tumour progression, remains unclear. Therefore, using a variety of nonmalignant and malignant cell lines and an organotypic raft-culture system, we investigated the relationship between HPV, gap junctions and tumour progression. Established cervical tumour cell lines carrying HPV were unable to communicate via gap junctions (when assayed by dye-transfer techniques). This correlated with lack of connexin protein expression, while transfection with connexins 26 or 43 led to functional gap junction membrane plaques. On the other hand, immortal but nonmalignant cell lines that contained episomal or integrated HPV-16, but required feeder-layer and growth-factor support, were consistently well coupled, and expressed multiple connexins at membrane junctions. In vitro selection of feeder-layer and growth-factorindependent variants eventually lead to loss of GJIC, which correlated with loss of membrane and increased cytoplasmic connexin 43 localization. However, this was preceded by loss of differentiation and stromal invasion, as assayed on the organotypic raft-culture model. Using this model, a comparison between noncoupled, well-coupled and connexin-transfected cell lines revealed no firm correlation between GJIC and dysplasia, but GJIC appeared to favour increased stratification. These findings demonstrate that loss of GJIC is frequent, but appears to occur more as a consequence of, rather than being the cause of, epithelial dysplasia, and may be influenced by, but is not directly attributable to, HPV.

show abstract

Section: Gjic-proficient Hela Cells Stably Transfected With Cx43contrasting

confidence: 56%

“…Further work also showed that premalignant conditions such as severe dysplasia have a dramatic decreased amount of gap junctions (McNutt et al, 1971). Immunohistochemistry of cervical biopsies shows reduced Cx43 expression in dysplastic regions compared to normal epithelia (King et al, 2000b).…”

Section: Introductionmentioning

confidence: 99%

The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression

et al. 2003

View full text Add to dashboard Cite

show abstract

“…They agreed with McNutt et al (1971), that in pre-malignant states there was a statistically significant decrease in the frequency of gap junctions. McNutt et al (1971) found few gap junctions in carcinoma in situ of the cervix but they reported poor temporal correlation between the development of severe gap junction deficiencies and tumour invasion. These findings sustained, however, the possibility that the loss of gap junctions is one of pre-requisites required for stromal invasion.…”

Section: Discussionsupporting

confidence: 78%

“…From these it has been found that the occurrence and development of different junctions appears to be related to the degree of tumour differentiation (Loevenstein, 1968;McNutt et al, 1971;Staehelin, 1974;Weinstein et al, 1976). Moreover, evaluation of the types of junctional complexes present in different tumours may also add to our knowledge about metastasis formation (McNutt et al, 1971;1976;Weinstein, 1976;Pauli et al, 1978).…”

mentioning

confidence: 99%

Intercellular junctions of methylcholanthrene-induced rat skin basocellular and squamous carcinomas

Horak¹,

Lelkes²,

Sugár³

1984

Br J Cancer

View full text Add to dashboard Cite

Summary The occurrence of different intercellular junctions in epithelial rat skin tumours induced by methylcholanthrene was investigated using thin sections and freeze-fracture replicas examined by electron microscopy. Tumours which appeared first were basal cell carcinomas. Later, different tumours of hair follicle and of sebaceous gland origin were formed. Finally, in the majority of tumours a squamous component evolved. Metastases developed from the squamous carcinomas exclusively.Desmosomes and gap junctions were detected in basal cell carcinomas whereas, in squamous carcinomas, tight junctions were also seen. While all three types of junction were found in the primary squamous tumours, the tumour metastases in lymph nodes and lungs contained only desmosomes.In earlier studies of the invasiveness and metastatic capacity of various tumours particular attention has been paid to the investigation of junctional complexes. From these it has been found that the occurrence and development of different junctions appears to be related to the degree of tumour differentiation (Loevenstein, 1968;McNutt et al., 1971;Staehelin, 1974;Weinstein et al., 1976). Moreover, evaluation of the types of junctional complexes present in different tumours may also add to our knowledge about metastasis formation (McNutt et al., 1971;1976;Weinstein, 1976;Pauli et al., 1978).The locally invasive human basal cell carcinoma grows slowly and exceptionally rarely forms metastases. The occurrence and structure of the junctional complexes well characterizes the different phases of invasive growth of these tumours (Posalaky et al., 1979).The pure forms of rat skin basocellular carcinomas are similar to the human examples in their morphological appearance and natural history. However, the frequent pilosebaceous differentiation and the simultaneously appearing squamous component in some experimentally induced skin neoplasms show that considerable differences exist (Zackheim, 1973;Sugar, 1981). The pure basal cell tumours never develop metastases, while in some cases of the later appearing squamous tumours, metastases appear in the regional lymph nodes or in the lungs.The objective of the present study was to ascertain whether the presence or absence of certain types of intercellular junctions could be correlated with the invasive or metastatic behaviour of different histological types of skin carcinomas. The junctional complexes of experimentally induced rat skin tumours and their metastases were examined by thin section electron microscopy as well as by freeze-fracture studies. Materials and methodsSkin tumours were induced in male Wistar rats by topical application of 3% methylcholanthrene, dissolved in acetone. The back skin of the animals was painted three times weekly for a year. The first lesions appeared in the sixth month after the beginning of treatment, as previously described by Sugar (1981). In this investigation we studied the sequential changes in the skin tumours of 96 animals by light microscopic investigation of 147 biopsies fro...

show abstract

“…In all these studies, however, only one type of gap junction has been reported interconnecting cells of the vertebrate myocardium (9), the mammalian liver (16,17), the cervical epithelium (22), the lateral giant nerve fibers of the crayfish (8,10), brown fat, and tissue culture cells (11,12). These results make it difficult to understand exactly how the intercellular flow of different types of regulatory molecules and small ions may be controlled.…”

Section: Discussionmentioning

confidence: 79%

Three Types of Gap Junctions Interconnecting Intestinal Epithelial Cells Visualized by Freeze-Etching

1972

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

108

View full text Add to dashboard Cite

Gap junctions are specialized membrane regions that seem to mediate intercellular communication. They appear to contain closely packed arrays of equally sized particles all of which, upon freeze-cleaving, remain attached to one membrane leaflet and not to the other. One gap junction cleavage face, therefore, always exhibits a closely packed array of particles, while the other features a corresponding array of pits. By using these morphological criteria, we have been able to distinguish three different types of gap junctions interlinking adjacent epithelial cells of the small intestine. All three types may be found in close proximity to each other, and in all cases, the particles remain attached to the cleavage face of the cytoplasmic membrane leaflet (A-face). The most frequently encountered type-I gap junctions, which have already been observed in many other tissues, possess 8- to 9-nm (80- to 90-Å) particles with a center-to-center spacing of 9-10 nm (90-100 Å) when packed in a hexagonal lattice. Type-II gap junctions are always found in close association with type-I junctions. They can be distinguished from the type-I junctions by the greater size [10-11 nm (100-110 Å) in diameter] and the greater spacing (190-200 Å) of their hexagonally arrayed particles. In contrast, the particles of the type-III gap junctions are arranged in very small rectilinear arrays with a spacing of only 6-8 nm (60-80 Å). Gap junctions may be involved in the control of intercellular flow of different types of regulatory molecules.

show abstract

Further Observations on the Occurrence of Nexuses in Benign and Malignant Human Cervical Epithelium

Cited by 126 publications

References 85 publications

The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression

The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression

Intercellular junctions of methylcholanthrene-induced rat skin basocellular and squamous carcinomas

Three Types of Gap Junctions Interconnecting Intestinal Epithelial Cells Visualized by Freeze-Etching

Contact Info

Product

Resources

About