An insight into cancer palaeobiology: does the Mesozoic neoplasm support tissue organization field theory of tumorigenesis?

BACKGROUND: Neoplasms are common across the animal kingdom and seem to be a feature plesiomorphic for metazoans, related with an increase in somatic complexity. The fossil record of cancer complements our knowledge of the origin of neoplasms and vulnerability of various vertebrate taxa. Here, we document the first undoubted record of primary malignant bone tumour in a Mesozoic non-amniote. The diagnosed osteosarcoma developed in the vertebral intercentrum of a temnospondyl amphibian, Metoposaurus krasiejowensis from the Krasiejów locality, southern Poland. RESULTS: A wide array of data collected from gross anatomy, histology, and microstructure of the affected intercentrum reveals the tumour growth dynamics and pathophysiological aspects of the neoplasm formation on the histological level. The pathological process almost exclusively pertains to the periosteal part of the bone composed from a highly vascularised tissue with lamellar matrix. The unorganised arrangement of osteocyte lacunae observed in the tissue is characteristic for bone tissue types connected with static osteogenesis, and not for lamellar bone. The neoplastic bone mimics on the structural level the fast growing fibrolamellar bone, but on the histological level develops through a novel ossification type. The physiological process of bone remodelling inside the endochondral domain continued uninterrupted across the pathology of the periosteal part. CONCLUSIONS: Based on the results, we discuss our case study's consistence with the Tissue Organization Field Theory of tumorigenesis, which locates the causes of neoplastic transformations in disorders of tissue architecture.

To be or not to be heavier: The role of dermal bones in the buoyancy of the Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis.

Stereospondyli are a clade of large aquatic temnospondyls known to have evolved a large dermal pectoral girdle. Among the Stereospondyli, metoposaurids in particular possess large interclavicles and clavicles relative to the rest of the postcranial skeleton. Because of the large size of these dermal bones, it was first proposed that they served as ballast during hydrostatic buoyancy control which assisted metoposaurids to live a bottom-dwelling mode of life. However, a large bone need not necessarily be heavy, for which determining the bone compactness becomes crucial for understanding any such adaptation in these dermal bones. Previous studies on the evolution of bone adaptations to aquatic lifestyles such as osteosclerosis, pachyostosis, osteoporotic-like pattern and pachyosteosclerosis have been observed in the long bones of secondarily aquatic amniotes. However, there are no known studies on the analysis of bone compactness in the dermal pectoral girdle of non-amniote taxa including Temnospondyli. This study looks at evidence of changes in bone mass adaptations in the dermal bones of the pectoral girdle of two stereospondyls occurring in the Late Triassic Krasiejόw locality (Southwestern Poland), namely: Metoposaurus krasiejowensis and Cyclotosaurus intermedius. However, because of lack of research on bone compactness of temnospondyls in general, there is no existent frame of reference to infer bone mass increase (BMI) in the M. krasiejowensis samples, and thus the bone compactness results of this taxon are compared with that of the samples of C. intermedius. Results of this study indicate that the interclavicles of M. krasiejowensis partially evolved BMI-like condition rendering these bones to be heavy enough to get selected as ballast during hydrostatic buoyancy control. Additionally, M. krasiejowensis shared its habitat with C. intermedius, however, the dermal pectoral girdle sample of the latter taxon does not display signs of BMI-like condition. Furthermore, the absence of variation in hydrostatic buoyancy control in the ontogenetic series of interclavicles of M. krasiejowensis could imply lack of ontogenetic niche shift along the water column.

Mandible histology in Metoposaurus krasiejowensis (Temnospondyli, Stereospondyli) from the Upper Triassic of Poland.

Recent studies that have systematically augmented our knowledge of dermal bones of the Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis have mostly focused on shoulder girdle elements and the skull. So far, histological data on the mandible are still scant. For the present study, two mandibles have been examined, using 50 standard thin sections. Dermal bones of the mandible reveal a uniform diploë structure, with the external cortex consisting of moderately vascularised, parallel-fibred bone, as well as a distinct alternation of thick zones and thinner annuli. Dense bundles of well-mineralised Sharpey's fibres are seen in the external cortex over the entire length of the mandible. The trabecular middle region is highly porous and well vascularised, showing small primary vascular canals and more numerous secondary osteons; irregular erosion spaces occur in large numbers as well. The thin and poorly vascular internal cortex consists of parallel-fibred bone. The articular is not a dermal bone in origin, having been formed of a thin layer of avascular cortex and a very extensive, trabecular middle region. In contrast to the dermal bones of the mandible, the articular developed from a cartilaginous precursor, as evidenced by numerous remains of calcified cartilage in the central parts of the bone. Histological variability is extremely high along the mandible, its anterior part being characterised by high compactness and biomechanically good resistance in contrast to the highly porous posterior parts. Distinct variations of bone thickness and degree of bone porosity in specific areas of the mandible, may be due to local differences in biomechanics during feeding. The microstructure of the mandible corroborates a previous study of the active and ambush predation strategy in metoposaurids.

Climatic influence on the growth pattern of Panthasaurus maleriensis from the Late Triassic of India deduced from paleohistology.

Metoposaurids are representatives of the extinct amphibian clade Temnospondyli, found on almost every continent exclusively in the Late Triassic deposits. Osteohistologically, it is one of the best-known temnospondyl groups, analyzed with a wide spectrum of methods, such as morphology, morphometry, bone histology or computed modelling. The least known member of Metoposauridae is Panthasaurus maleriensis from the Pranhita-Godavari basin in Central India, being geographically the most southern record of this family. For the first time the bone histology of this taxon was studied with a focus on the intraspecific variability of the histological framework and the relationship between the observed growth pattern and climatic and/or environmental conditions. The studied material includes thin-sections of five long bones, a rib, an ilium and an intercentrum belonging most likely to eight individuals ranging from different ontogenetic stages. All bones have a large medullary region with progressively increasing remodeling, surrounded by a lamellar-zonal tissue type. The primary cortex consists of parallel-fibered matrix showing various degrees of organization, less organized collagen fibers in the zones and higher organized in the annuli. Growth marks occur in the form of alternating zones and annuli in every bone except the ilium and the intercentrum. The vascularity becomes less dense towards the outermost cortex in all sampled limb bones. Towards the outermost cortex the zone thickness is decreasing, in contrast to the avascular annuli, that become thicker or are of the same thickness. The growth pattern of P. maleriensis is uniform and represents changes in ontogenetic development. Multiple resting lines are prominent in the outer annuli of the limb bones and the rib and they presumably indicate climatic and environmental influence on the growth pattern. Therefore, a prolonged phase of slowed-down growth occurred during the unfavorable phase, but a complete cessation of growth indicated by Lines of Arrested Growth (LAGs) is not recorded in the studied samples. Based on the histological framework we conclude that the climate had an impact on the growth pattern. As we do not see any LAGs in the Indian metoposaurid, we assume that the local climate was relatively mild in India during the Late Triassic. A similar prolonged phase of slowed down growth without the occurrence of LAGs was observed in Metoposaurus krasiejowensis from the Late Triassic of Krasiejów (Poland). This is in contrast to Moroccan metoposaurid Dutuitosaurus ouazzoui from the Late Triassic of Argana Basin, where LAGs are regularly deposited throughout ontogeny indicating most likely harsher climatic conditions.

Pentadactyl manus of the Metoposaurus krasiejowensis from the Late Triassic of Poland, the first record of pentadactyly among Temnospondyli.

Temnospondyli are commonly believed to have possessed four digits in the manus and five in the pes. However, actual finds of articulated autopodia are extremely rare. Therefore, an articulated, slightly incomplete forelimb skeleton with preserved manus of Metoposaurus krasiejowensis from the Late Triassic of Poland is important in providing new details about the structure and ossification sequence in the temnospondyl limb. The most important observation is the presence of five metacarpals in this specimen. This allows reconstructing the manus as pentadactyl. The number of phalanges and the distribution of distal articulation facets allow reconstruction of the digit formula as (2?)-3-3-(3?)-(2?). The well-developed fifth digit suggests that the Metoposaurus manus shows a unique ossification sequence: the reduction or late ossification of the first digit conforms to the amniote-frog pattern, and the early development of the second and third digit makes Metoposaurus similar to salamanders. Based on the distribution of pentadactyly vs. tetradactyly in the temnospondyl manus, the number of digits was not phylogenetically constrained in temnospondyls, similar to today's amphibians.

Cranial suture biomechanics in Metoposaurus krasiejowensis (Temnospondyli, Stereospondyli) from the upper Triassic of Poland.

Cranial sutures connect adjacent bones of the skull and play an important role in the absorption of stresses that may occur during different activities. The Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis has been extensively studied over the years in terms of skull biomechanics, but without a detailed description of the function of cranial sutures. In the present study, 34 thin sections of cranial sutures were examined in order to determine their histovariability and interpret their biomechanical role in the skull. The histological model was compared with three-dimensional-finite element analysis (FEA) simulations of the skull under bilateral and lateral biting as well as skull-raising loads for maximum and minimum principal stress. Histologically, only two sutural morphologies were recognised in the skull of Metoposaurus: interdigitated sutures (commonly associated with compressive stresses) are dominant along the entire length of the skull roof and palate; tongue-and-groove sutures (commonly associated with tensile stresses) are present across the maxilla. FEA shows a much more complex picture of stress type and distribution than predicted by sutures. Common to both methods is a predominance of compressive stresses which act on the skull during biting. The methods predict different stress regimes during biting in the posterior part of the skull: where histological analysis suggests compression, FEA predicts tension. For lateral biting and skull raising, histological and digital reconstructions show similar general patterns but with some variations.

Merging cranial histology and 3D-computational biomechanics: a review of the feeding ecology of a Late Triassic temnospondyl amphibian.

Finite Element Analysis (FEA) is a useful method for understanding form and function. However, modelling of fossil taxa invariably involves assumptions as a result of preservation-induced loss of information in the fossil record. To test the validity of predictions from FEA, given such assumptions, these results could be compared to independent lines of evidence for cranial mechanics. In the present study a new concept of using bone microstructure to predict stress distribution in the skull during feeding is put forward and a correlation between bone microstructure and results of computational biomechanics (FEA) is carried out. The bony framework is a product of biological optimisation; bone structure is created to meet local mechanical conditions. To test how well results from FEA correlate to cranial mechanics predicted from bone structure, the well-known temnospondyl Metoposaurus krasiejowensis was used as a model. A crucial issue to Temnospondyli is their feeding mode: did they suction feed or employ direct biting, or both? Metoposaurids have previously been characterised either as active hunters or passive bottom dwellers. In order to test the correlation between results from FEA and bone microstructure, two skulls of Metoposaurus were used, one modelled under FE analyses, while for the second one 17 dermal bone microstructure were analysed. Thus, for the first time, results predicting cranial mechanical behaviour using both methods are merged to understand the feeding strategy of Metoposaurus. Metoposaurus appears to have been an aquatic animal that exhibited a generalist feeding behaviour. This taxon may have used two foraging techniques in hunting; mainly bilateral biting and, to a lesser extent, lateral strikes. However, bone microstructure suggests that lateral biting was more frequent than suggested by Finite Element Analysis (FEA). One of the potential factors that determined its mode of life may have been water levels. During optimum water conditions, metoposaurids may have been more active ambush predators that were capable of lateral strikes of the head. The dry season required a less active mode of life when bilateral biting is particularly efficient. This, combined with their characteristically anteriorly positioned orbits, was optimal for ambush strategy. This ability to use alternative modes of food acquisition, independent of environmental conditions, might hold the key in explaining the very common occurrence of metoposaurids during the Late Triassic.

Feeding biomechanics of Late Triassic metoposaurids (Amphibia: Temnospondyli): a 3D finite element analysis approach.

The Late Triassic freshwater ecosystems were occupied by different tetrapod groups including large-sized anamniotes, such as metoposaurids. Most members of this group of temnospondyls acquired gigantic sizes (up to 5 m long) with a nearly worldwide distribution. The paleoecology of metoposaurids is controversial; they have been historically considered passive, bottom-dwelling animals, waiting for prey on the bottom of rivers and lakes, or they have been suggested to be active mid-water feeders. The present study aims to expand upon the paleoecological interpretations of these animals using 3D finite element analyses (FEA). Skulls from two taxa, Metoposaurus krasiejowensis, a gigantic taxon from Europe, and Apachesaurus gregorii, a non-gigantic taxon from North America, were analyzed under different biomechanical scenarios. Both 3D models of the skulls were scaled to allow comparisons between them and reveal that the general stress distribution pattern found in both taxa is clearly similar in all scenarios. In light of our results, both previous hypotheses about the paleoecology of these animals can be partly merged: metoposaurids probably were ambush and active predators, but not the top predators of these aquatic environments. The FEA results demonstrate that they were particularly efficient at bilateral biting, and together with their characteristically anteropositioned orbits, optimal for an ambush strategy. Nonetheless, the results also show that these animals were capable of lateral strikes of the head, suggesting active hunting of prey. Regarding the important skull size differences between the taxa analyzed, our results suggest that the size reduction in the North American taxon could be related to drastic environmental changes or the increase of competitors. The size reduction might have helped them expand into new ecological niches, but they likely remained fully aquatic, as are all other metoposaurids.

Cranial bone histology of Metoposaurus krasiejowensis (Amphibia, Temnospondyli) from the Late Triassic of Poland.

In this study, 21 skull bones of Metoposaurus krasiejowensis from the Late Triassic of Poland were investigated histologically. Dermal bones show a diploë structure, with an ornamented external surface. The ridges consist of mostly well vascularized parallel-fibered bone; the valleys are built of an avascular layer of lamellar bone. The thick middle region consists of cancellous bone, with varying porosity. The thin and less vascularized internal cortex consists of parallel-fibered bone. The numerous Sharpey's fibers and ISF are present in all bones. The cyclicity of growth is manifested as an alternation of thick, avascular annuli and high vascularized zones as well as a sequence of resting lines. The detailed histological framework of dermal bones varies even within a single bone; this seems to be related to the local biomechanical loading of the particular part of the skull. The dynamic processes observed during the ornamentation creation indicate that the positions of the ridges and grooves change during growth and could be a specific adaptation to changing biomechanical conditions and stress distribution during bone development. In the supratemporal, the cementing lines show that the remodeling process could be involved in the creations of sculpture. The common occurrence of ISF suggests that metaplastic ossification plays an important role during cranial development. Endochondral bones preserved the numerous remains of calcified cartilage. This indicates that ossification follows a pattern known for stereospondyl intercentra, with relatively slow ossification of the trabecular part and late development of the periosteal cortex. The large accumulation of Sharpey's fibers in the occipital condyles indicates the presence of strong muscles and ligaments connecting the skull to the vertebral column.