Regional Differences in the Growth of Normal and Neoplastic Cells

Auerbach, Robert; Auerbach, Wanda

doi:10.1126/science.7053564

Cited by 87 publications

(35 citation statements)

References 47 publications

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“…Another possibility is that the propensity of neoblasts to respond to gap junction-mediated signal differs in a graded manner along the AP axis. This AP progression confirms the existence of AP gradients that were hypothesized to exist by classical workers in the regeneration field (Brondsted, 1969), provides a molecular entry-point into the known but still not understood relationship between position along the AP axis and proliferation rates of neoplastic and normal cells in mammals (Auerbach and Auerbach, 1982), and suggests that a primary component of physiological gradients are the neoblasts themselves. These data additionally demonstrate that the control of neoblast proliferation by gap junction signals functionally interacts with the morphogenetic polarity of the animal; future work must address the mechanisms integrating neoblast behavior with large-scale axial patterning.…”

Section: Discussionsupporting

confidence: 60%

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

Oviedo¹,

Levin²

2007

Development

104

102

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The largely unknown mechanisms that regulate adult stem cells probably involve signals from neighboring differentiated cells. Gap junction channels providing direct cell-cell communication via small molecules are a crucial component of morphogenesis and normal physiology. However, no specific gap junction protein has yet been functionally linked to adult/somatic stem cell behavior in vivo or to organ regeneration. We report the identification and characterization of smedinx-11 -an innexin gap junction channel gene expressed in the adult stem cells (neoblasts) of the planarian Schmidtea mediterranea. smedinx-11 RNAi treatment inhibits regeneration and abrogates neoblast maintenance. Moreover, smedinx-11 expression is enriched in an irradiation-sensitive subpopulation ('X2') and is required for proper expression of other stem cell-specific markers. Analyses of the smedinx-11 downregulation phenotype revealed a striking anterior-posterior neoblast gradient. Our data demonstrate a novel role for gap junction proteins and suggest gap junction-mediated signaling as a new and tractable control point for adult, somatic stem cell regulation.

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Section: Discussionsupporting

confidence: 60%

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

Oviedo¹,

Levin²

2007

Development

104

102

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“…These observations were consistent with anterior-to-posterior differences in tumor growth rate described in spontaneous mammary cancer models (24). To select a reproducible source of mammary tumors, we compared the growth of paired tumor fragments arising from anterior (axillary) mammary glands with posterior (inguinal) mammary glands obtained from the same PyMT mice.…”

Section: Selection Of Mammary Tumor Tissues For Transplantationsupporting

confidence: 65%

Accelerated Preclinical Testing Using Transplanted Tumors from Genetically Engineered Mouse Breast Cancer Models

Varticovski

Hollingshead

Robles

et al. 2007

Clinical Cancer Research

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Purpose: The use of genetically engineered mouse (GEM) models for preclinical testing of anticancer therapies is hampered by variable tumor latency, incomplete penetrance, and complicated breeding schemes. Here, we describe and validate a transplantation strategy that circumvents some of these difficulties. Experimental Design: Tumor fragments from tumor-bearing MMTV-PyMTor cell suspensions from MMTV-PyMT, -Her2/neu, -wnt1, -wnt1/p53 +/À , BRCA1/p53, and C3(1)T-Ag mice were transplanted into the mammary fat pad or s.c. into naI« ve syngeneic or immunosuppressed mice. Tumor development was monitored and tissues were processed for histopathology and gene expression profiling. Metastasis was scored 60 days after the removal of transplanted tumors. Results: PyMT tumor fragments and cell suspensions from anterior glands grew faster than posterior tumors in serial passages regardless of the site of implantation. Microarray analysis revealed genetic differences between these tumors. The transplantation was reproducible using anterior tumors from multiple GEM, and tumor growth rate correlated with the number of transplanted cells. Similar morphologic appearances were observed in original and transplanted tumors. Metastasis developed in >90% of mice transplanted with PyMT, 40% with BRCA1/ p53 +/À and wnt1/p53 +/À , and 15% with Her2/neu tumors. Expansion of PyMTand wnt1tumors by serial transplantation for two passages did not lead to significant changes in gene expression. PyMT-transplanted tumors and anterior tumors of transgenic mice showed similar sensitivities to cyclophosphamide and paclitaxel. Conclusions: Transplantation of GEM tumors can provide a large cohort of mice bearing mammary tumors at the same stage of tumor development and with defined frequency of metastasis in a well-characterized molecular and genetic background.

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“…In mice, cellular proliferation and engraftment responses are superior in the anterior region of the body (i.e. head and thoracic cavity) to those in posterior areas (Auerbach and Auerbach, 1982;Kobayashi, 1977). Likewise, the effects of carcinogens and the growth of transplanted tumor cells are more aggressive in the anterior than in the posterior regions (Auerbach and Auerbach, 1982;Auerbach et al, 1978;Dispersio, 1981;Kubai and Auerbach, 1980).…”

Section: Introductionmentioning

confidence: 99%

“…The proliferative response of normal and neoplastic cells is influenced by their topographical location along the anteroposterior axis (Auerbach and Auerbach, 1982). In mice, cellular proliferation and engraftment responses are superior in the anterior region of the body (i.e.…”

Section: Introductionmentioning

confidence: 99%

Regional signals in the planarian body guide stem cell fate in the presence of DNA instability

et al. 2016

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Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. We identified a regional switch in the adult planarian body upon systemic disruption of homologous recombination with RNAinterference of Rad51. Rad51 knockdown increases DNA doublestrand breaks (DSBs) throughout the body, but stem cells react differently depending on their location along the anteroposterior axis. In the presence of extensive DSBs, cells in the anterior part of the body resist death, whereas cells in the posterior region undergo apoptosis. Furthermore, we found that proliferation of cells with DNA damage is induced in the presence of brain tissue and that the retinoblastoma pathway enables overproliferation of cells with DSBs while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators of regional cell behavior and cellular transformation in the adult body.

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Regional Differences in the Growth of Normal and Neoplastic Cells

Cited by 87 publications

References 47 publications

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

Accelerated Preclinical Testing Using Transplanted Tumors from Genetically Engineered Mouse Breast Cancer Models

Regional signals in the planarian body guide stem cell fate in the presence of DNA instability

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